hydrolases

Summary

Summary: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., ESTERASES, glycosidases (GLYCOSIDE HYDROLASES), lipases, NUCLEOTIDASES, peptidases (PEPTIDE HYDROLASES), and phosphatases (PHOSPHORIC MONOESTER HYDROLASES). EC 3.

Top Publications

  1. pmc A classification of glycosyl hydrolases based on amino acid sequence similarities
    B Henrissat
    Centre de Recherches sur les Macromolecules Vegetales, C N R S, Grenoble, France
    Biochem J 280:309-16. 1991
  2. pmc Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation
    Yanming Wang
    Center for Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA
    J Cell Biol 184:205-13. 2009
  3. pmc N-α-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide, a protein arginine deiminase inhibitor, reduces the severity of murine collagen-induced arthritis
    Van C Willis
    Division of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA
    J Immunol 186:4396-404. 2011
  4. pmc PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps
    Pingxin Li
    Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA
    J Exp Med 207:1853-62. 2010
  5. ncbi PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease
    Erik R Vossenaar
    Department of Biochemistry, University of Nijmegen, Nijmegen, The Netherlands
    Bioessays 25:1106-18. 2003
  6. pmc Regulation of p53 target gene expression by peptidylarginine deiminase 4
    Pingxin Li
    Center for Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA
    Mol Cell Biol 28:4745-58. 2008
  7. pmc Arginine deprivation as a targeted therapy for cancer
    L Feun
    Hematology Oncology, University of Miami School of Medicine, 1201 N W 16th Street, Miami, FL 33136, USA
    Curr Pharm Des 14:1049-57. 2008
  8. ncbi Alkali production by oral bacteria and protection against dental caries
    R A Burne
    Center for Oral Biology and Department of Microbiology and Immunology, University of Rochester Medical Center, Box 611, 601 Elmwood Ave, Rochester, NY 14642, USA
    FEMS Microbiol Lett 193:1-6. 2000
  9. pmc Potential role for PAD2 in gene regulation in breast cancer cells
    Brian D Cherrington
    Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming, United States of America
    PLoS ONE 7:e41242. 2012
  10. pmc Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis
    Randie H Kim
    Department of Biological Chemistry, Division of Surgical Oncology, Center for Biophotonics and Science Technology, University of California at Davis, Sacramento, California 95817, USA
    Cancer Res 69:700-8. 2009

Detail Information

Publications349 found, 100 shown here

  1. pmc A classification of glycosyl hydrolases based on amino acid sequence similarities
    B Henrissat
    Centre de Recherches sur les Macromolecules Vegetales, C N R S, Grenoble, France
    Biochem J 280:309-16. 1991
    The amino acid sequences of 301 glycosyl hydrolases and related enzymes have been compared. A total of 291 sequences corresponding to 39 EC entries could be classified into 35 families...
  2. pmc Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation
    Yanming Wang
    Center for Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA
    J Cell Biol 184:205-13. 2009
    ..Together, these results suggest that histone hypercitrullination has important functions in chromatin decondensation in granulocytes/neutrophils...
  3. pmc N-α-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide, a protein arginine deiminase inhibitor, reduces the severity of murine collagen-induced arthritis
    Van C Willis
    Division of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA
    J Immunol 186:4396-404. 2011
    ..Cl-amidine may represent a novel class of disease-modifying agents that modulate aberrant citrullination, and perhaps other immune processes, necessary for the development of inflammatory arthritis...
  4. pmc PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps
    Pingxin Li
    Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA
    J Exp Med 207:1853-62. 2010
    ..Our results define a role for histone hypercitrullination in innate immunity during bacterial infection...
  5. ncbi PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease
    Erik R Vossenaar
    Department of Biochemistry, University of Nijmegen, Nijmegen, The Netherlands
    Bioessays 25:1106-18. 2003
    ..This article contains supplementary material which may be viewed at the BioEssays website at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/2003/25/v25.1106.html...
  6. pmc Regulation of p53 target gene expression by peptidylarginine deiminase 4
    Pingxin Li
    Center for Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA
    Mol Cell Biol 28:4745-58. 2008
    ..The dynamics of RNA Pol II activities after UV treatment were further corroborated by permanganate footprinting. Together, these results suggest a role of PAD4 in the regulation of p53 target gene expression...
  7. pmc Arginine deprivation as a targeted therapy for cancer
    L Feun
    Hematology Oncology, University of Miami School of Medicine, 1201 N W 16th Street, Miami, FL 33136, USA
    Curr Pharm Des 14:1049-57. 2008
    ..This article reviews our laboratory and clinical experience as well as that from others with ADI-PEG20 as an antineoplastic agent. Future direction in utilizing this agent is also discussed...
  8. ncbi Alkali production by oral bacteria and protection against dental caries
    R A Burne
    Center for Oral Biology and Department of Microbiology and Immunology, University of Rochester Medical Center, Box 611, 601 Elmwood Ave, Rochester, NY 14642, USA
    FEMS Microbiol Lett 193:1-6. 2000
    ..This short review highlights recent progress on understanding molecular genetic and physiologic aspects of ammonia generation by prominent oral bacteria...
  9. pmc Potential role for PAD2 in gene regulation in breast cancer cells
    Brian D Cherrington
    Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming, United States of America
    PLoS ONE 7:e41242. 2012
    ..Thus, our findings define a novel role for PAD2 in gene expression in human mammary epithelial cells...
  10. pmc Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis
    Randie H Kim
    Department of Biological Chemistry, Division of Surgical Oncology, Center for Biophotonics and Science Technology, University of California at Davis, Sacramento, California 95817, USA
    Cancer Res 69:700-8. 2009
    ..Finally, a tissue microarray of 88 prostate tumor samples lacked expression of ASS, indicating ADI-PEG20 is a potential novel therapy for the treatment of prostate cancer..
  11. pmc Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis
    Hongjie Yao
    Center for Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA
    J Biol Chem 283:20060-8. 2008
    ..Together, our studies identify OKL38 as a novel p53 target gene that is regulated by PAD4 and plays a role in apoptosis...
  12. pmc Suppression of colitis in mice by Cl-amidine: a novel peptidylarginine deiminase inhibitor
    Alexander A Chumanevich
    Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, 29208, USA
    Am J Physiol Gastrointest Liver Physiol 300:G929-38. 2011
    ..In total, these data help validate the PADs as therapeutic targets for the treatment of IBD and further suggest Cl-amidine as a candidate therapy for this disease...
  13. ncbi Bioinformatics and molecular modeling in chemical enzymology. Active sites of hydrolases
    S D Varfolomeev
    School of Chemistry, Lomonosov Moscow State University, Moscow, Russia
    Biochemistry (Mosc) 67:1099-108. 2002
    ..structural substitutions of conservative and non-conservative glycines and their effects on geometry of catalytic site of typical hydrolases. The substitution of glycine(s) for alanine significantly altered the catalytic site structures.
  14. ncbi Alpha/Beta-hydrolase fold enzymes: structures, functions and mechanisms
    M Holmquist
    Department of Biotechnology, Royal Institute of Technology, SE 100 44 Stockholm, Sweden
    Curr Protein Pept Sci 1:209-35. 2000
    ..Relationships between active site anatomy, topology and conformational rearrangements in the protein molecule is discussed in the context of enzyme mechanism of action...
  15. ncbi Citrullination: a posttranslational modification in health and disease
    Bence György
    Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary
    Int J Biochem Cell Biol 38:1662-77. 2006
    ..We review the citrullinated peptide epitopes that are proposed as disease markers, specifically recognized in certain human autoimmune disorders. The potential autopathogenic role of citrullinated epitopes is also discussed...
  16. pmc Activity-based proteomics of enzyme superfamilies: serine hydrolases as a case study
    Gabriel M Simon
    Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 285:11051-5. 2010
    ..protein profiling and its implementation to annotate the enzymatic proteome, with particular attention given to probes that target serine hydrolases, a diverse superfamily of enzymes replete with many uncharacterized members.
  17. pmc Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase
    W T McGraw
    Department of Biochemistry, University of Georgia, Athens, Georgia 30602, USA
    Infect Immun 67:3248-56. 1999
    ..gingivalis, promotes the growth of the pathogen in the periodontal pocket, initially by enhancing its survivability and then by assisting the organism in its circumvention of host humoral defenses...
  18. ncbi Evolutionary genomics of the HAD superfamily: understanding the structural adaptations and catalytic diversity in a superfamily of phosphoesterases and allied enzymes
    A Maxwell Burroughs
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
    J Mol Biol 361:1003-34. 2006
    ..The newly identified relationships and functional predictions provided here are likely to aid the future exploration of the numerous poorly understood members of this large superfamily of enzymes...
  19. ncbi Nuclear localization of peptidylarginine deiminase V and histone deimination in granulocytes
    Katsuhiko Nakashima
    Graduate School of Integrated Science, Yokohama City University, 22 2 Seto, Kanazawa Ku, Yokohama 236 0027, Japan
    J Biol Chem 277:49562-8. 2002
    ..The major deiminated proteins were identified as histones H2A, H3, and H4. The implication of PAD V in histone modifications is discussed...
  20. pmc Arginine deiminase PEG20 inhibits growth of small cell lung cancers lacking expression of argininosuccinate synthetase
    M P Kelly
    Ludwig Institute for Cancer Research Ltd, New York Branch of Human Cancer Immunology at Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Br J Cancer 106:324-32. 2012
    ..Arginine deiminase (ADI) is a microbial enzyme capable of efficiently depleting peripheral blood arginine...
  21. pmc Protein arginine deiminase 4: a target for an epigenetic cancer therapy
    Jessica L Slack
    Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
    Cell Mol Life Sci 68:709-20. 2011
    ..Taken together, these findings suggest PAD4 inhibition as a novel epigenetic approach for the treatment of cancer, and suggest that F- and Cl-amidine are candidate therapeutic agents for this disease...
  22. pmc Potential role for peptidylarginine deiminase 2 (PAD2) in citrullination of canine mammary epithelial cell histones
    Brian D Cherrington
    J A Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America
    PLoS ONE 5:e11768. 2010
    ..This observation supports the hypothesis that PAD2 may play a regulatory role in the expression of lactation related genes via histone citrullination during diestrus...
  23. ncbi Food applications of bacterial cell wall hydrolases
    Lien Callewaert
    Centre for Food and Microbial Technology, Katholieke Universiteit Leuven, Kasteelpark Arenberg 23 box 2457, B 3001 Leuven, Belgium
    Curr Opin Biotechnol 22:164-71. 2011
    Bacterial cell wall hydrolases (BCWHs) display a remarkable structural and functional diversity that offers perspectives for novel food applications, reaching beyond those of the archetype BCWH and established biopreservative hen egg ..
  24. ncbi Crystal structure of Escherichia coli thioesterase I/protease I/lysophospholipase L1: consensus sequence blocks constitute the catalytic center of SGNH-hydrolases through a conserved hydrogen bond network
    Yu Chih Lo
    Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Neihu 114, Taiwan
    J Mol Biol 330:539-51. 2003
    ..O=C hydrogen bond usually plays a role in the catalytic mechanisms of most serine hydrolases, however, there were none present in SGNH-hydrolases...
  25. pmc Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization
    Yuan Luo
    Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, South Carolina 29208, USA
    Biochemistry 45:11727-36. 2006
    ..In addition, they represent potential lead compounds for the treatment of rheumatoid arthritis because a growing body of evidence supports a role for PAD4 in the onset and progression of this chronic autoimmune disorder...
  26. ncbi Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity. Application of an iterative approach to database search
    E V Koonin
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894
    J Mol Biol 244:125-32. 1994
    ..and with alignment blocks, we show that bacterial haloacid dehalogenases (HADs) belong to a large superfamily of hydrolases with diverse substrate specificity...
  27. ncbi Structural basis for Ca(2+)-induced activation of human PAD4
    Kyouhei Arita
    Graduate School of Integrated Science, Yokohama City University, 1 7 29 Suehiro cho, Tsurumi ku, Yokohama 230 0045, Japan
    Nat Struct Mol Biol 11:777-83. 2004
    ..Our findings identify a novel mechanism for enzyme activation by Ca(2+) ions, and are important for understanding the mechanism of protein citrullination and for developing PAD-inhibiting drugs for the treatment of rheumatoid arthritis...
  28. ncbi Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies
    Francesco Izzo
    Pascale NAtional Cancer Institute, Naples, Italy
    J Clin Oncol 22:1815-22. 2004
    ..The study was a cohort dose-escalation phase I/II study...
  29. ncbi Citrullination by peptidylarginine deiminase in rheumatoid arthritis
    Akari Suzuki
    Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research RIKEN, 1 7 22, Suehirocho, Tsurumi ku, Yokohama City, Kanagawa, Japan
    Ann N Y Acad Sci 1108:323-39. 2007
    ..This review summarizes the relationship between RA and citrullination, as well as the role of PADI4 genetics...
  30. ncbi Novel alternatives to antibiotics: bacteriophages, bacterial cell wall hydrolases, and antimicrobial peptides
    A Parisien
    Department of Chemical Engineering, University of Ottawa, Ottawa, Canada
    J Appl Microbiol 104:1-13. 2008
    ..occurring antimicrobials as novel alternatives to antibiotics: bacteriophages (phages), bacterial cell wall hydrolases (BCWH), and antimicrobial peptides (AMP)...
  31. ncbi Pegylated arginine deiminase (ADI-SS PEG20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo
    Charles Mark Ensor
    Department of Biology, T H Morgan Building and Phoenix Pharmacologics, Inc, Lexington, Kentucky 40503, USA
    Cancer Res 62:5443-50. 2002
    ....
  32. pmc Coordination of PAD4 and HDAC2 in the regulation of p53-target gene expression
    P Li
    Department of Biochemistry and Molecular Biology, Center for Eukaryotic Gene Regulation, Pennsylvania State University, University Park, PA 16802, USA
    Oncogene 29:3153-62. 2010
    ..Our results unveil an important crosstalk between histone deacetylation and citrullination, suggesting that a combination of PAD4 and HDAC2 inhibitors as a potential strategy for cancer treatment...
  33. ncbi Phase II study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma
    Evan S Glazer
    Department of Surgical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX, USA
    J Clin Oncol 28:2220-6. 2010
    ..This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, alpha-fetoprotein (AFP) levels, and serum arginine levels...
  34. ncbi Pegylated arginine deiminase treatment of patients with metastatic melanoma: results from phase I and II studies
    Paolo A Ascierto
    Pascale NAtional Cancer Institute, Naples, Italy
    J Clin Oncol 23:7660-8. 2005
    ..A novel amino acid-degrading enzyme (arginine deiminase) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) was used to lower plasma arginine in individuals with metastatic melanoma...
  35. pmc Identification of plant cell wall mutants by means of a forward chemical genetic approach using hydrolases
    Sascha Gille
    Department of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA
    Proc Natl Acad Sci U S A 106:14699-704. 2009
    A previously undescribed forward chemical genetic screen using hydrolases affecting the extracellular matrix is introduced...
  36. ncbi Activity-based protein profiling: from enzyme chemistry to proteomic chemistry
    Benjamin F Cravatt
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Annu Rev Biochem 77:383-414. 2008
    ..Here, we review the basic technology of ABPP, the enzyme classes addressable by this method, and the biological discoveries attributable to its application...
  37. pmc Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells
    Emma Ringqvist
    Department of Cell and Molecular Biology, BMC, Uppsala University, Uppsala, Sweden
    Mol Biochem Parasitol 159:85-91. 2008
    ..These results indicate that contact of Giardia with epithelial cells triggers metabolic enzyme release, which might facilitate effective colonization of the human small intestine...
  38. pmc Cell wall hydrolases affect germination, vegetative growth, and sporulation in Streptomyces coelicolor
    Henry J Haiser
    Department of Biology and Michael G DeGroote Institute for Infectious Disease Research, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada
    J Bacteriol 191:6501-12. 2009
    ..coelicolor, highlighting both the lack of redundancy in hydrolase activity and the importance of cell wall remodeling in the S. coelicolor life cycle...
  39. ncbi Probing enzyme promiscuity of SGNH hydrolases
    Ivana Leščić Ašler
    Department of Physical Chemistry, Rudjer Boskovic Institute, 10002 Zagreb, Croatia
    Chembiochem 11:2158-67. 2010
    Several hydrolases of the SGNH superfamily, including the lipase SrLip from Streptomyces rimosus (Q93MW7), the acyl-CoA thioesterase I TesA from Pseudomonas aeruginosa (Q9HZY8) and the two lipolytic enzymes EstA (from P...
  40. ncbi Peptidylarginine deiminase modulates the physiological roles of enolase via citrullination: links between altered multifunction of enolase and neurodegenerative diseases
    Byungki Jang
    Ilsong Institute of Life Science, Hallym University, 1605 4 Gwanyang dong, Dongan Gu, Anyang, Gyeonggi do 432 060, Republic of Korea
    Biochem J 445:183-92. 2012
    ..These findings suggest that PAD-mediated citrullination regulates the diverse physiological activities of enolase and that CE may be a candidate diagnostic/prognostic factor for degenerative diseases...
  41. pmc Biochemical characterization of a novel haloalkane dehalogenase from a cold-adapted bacterium
    Ivana Drienovska
    Loschmidt Laboratories, Department of Experimental Biology and Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Brno, Czech Republic
    Appl Environ Microbiol 78:4995-8. 2012
    ..DpcA exhibited a unique temperature profile with exceptionally high activities at low temperatures. The psychrophilic properties of DpcA make this enzyme promising for various environmental applications...
  42. ncbi Bacteriophage virion-associated peptidoglycan hydrolases: potential new enzybiotics
    Lorena Rodríguez-Rubio
    Instituto de Productos Lacteos de Asturias IPLA CSIC, Paseo Rio Linares sn Villaviciosa Asturias, Spain
    Crit Rev Microbiol 39:427-34. 2013
    Virion-associated peptidoglycan hydrolases (VAPGH) are phage-encoded lytic enzymes that locally degrade the peptidoglycan (PG) of the bacterial cell wall during infection...
  43. pmc CREST--a large and diverse superfamily of putative transmembrane hydrolases
    Jimin Pei
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA
    Biol Direct 6:37. 2011
    ..Recently, a group of putative transmembrane receptors called progestin and adipoQ receptors (PAQRs) were found to be distantly related to alkaline ceramidases, raising the possibility that they may also function as membrane enzymes...
  44. ncbi Haloalkane dehalogenases: biotechnological applications
    Tana Koudelakova
    Loschmidt Laboratories, Department of Experimental Biology and Research Centre for Toxic Compounds in the Environment, Masaryk University, Brno, Czech Republic
    Biotechnol J 8:32-45. 2013
    Haloalkane dehalogenases (EC 3.8.1.5, HLDs) are α/β-hydrolases which act to cleave carbon-halogen bonds...
  45. ncbi Correction of pathological accumulation of glycosaminoglycans in central nervous system and peripheral tissues of MPSIIIA mice through systemic AAV9 gene transfer
    Albert Ruzo
    Center of Animal Biotechnology and Gene Therapy, Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autonoma de Barcelona, 08193 Bellaterra, Spain
    Hum Gene Ther 23:1237-46. 2012
    ..Finally, correction of disease phenotype resulted in a remarkable prolongation of survival of both male and female AAV-treated MPSIIIA mice. This proof-of-concept study will be relevant to the future development of therapies for MPSIIIA...
  46. ncbi Directed evolution of hydrolases for prevention of G-type nerve agent intoxication
    Rinkoo D Gupta
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
    Nat Chem Biol 7:120-5. 2011
    ..We then demonstrated the in vivo prophylactic activity of an evolved variant. These evolved variants and the newly developed screens provide the basis for engineering PON1 for prophylaxis against other G-type agents...
  47. ncbi Increased citrullination of histone H3 in multiple sclerosis brain and animal models of demyelination: a role for tumor necrosis factor-induced peptidylarginine deiminase 4 translocation
    Fabrizio G Mastronardi
    Department of Structural Biology and Biochemistry, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8
    J Neurosci 26:11387-96. 2006
    ..In conclusion, high citrullination of histones consequent to PAD4 nuclear translocation is part of the process that leads to irreversible changes in oligodendrocytes and may contribute to apoptosis of oligodendrocytes in MS...
  48. pmc Crystal structure of trehalose-6-phosphate phosphatase-related protein: biochemical and biological implications
    Krishnamurthy N Rao
    Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA
    Protein Sci 15:1735-44. 2006
    ..We have confirmed that T6PP is a trehalose phosphatase from amino acid sequence, three-dimensional structure, and biochemical assays...
  49. ncbi Completing the purine utilisation pathway of Aspergillus nidulans
    Christos Gournas
    Faculty of Biology, Panepistemioupolis 15781, Athens, Greece
    Fungal Genet Biol 48:840-8. 2011
    ..The identification of these additional genes confirms the complete absence of clustering of the genes involved in purine utilisation in A. nidulans...
  50. ncbi Proteomics-based compositional analysis of complex cellulase-hemicellulase mixtures
    Shishir P S Chundawat
    Biomass Conversion Research Laboratory, Chemical Engineering and Materials Science, Michigan State University, 3815 Technology Boulevard, Suite 1045, Lansing, Michigan 48910, United States
    J Proteome Res 10:4365-72. 2011
    ....
  51. ncbi Protein deiminases: new players in the developmentally regulated loss of neural regenerative ability
    Sigrun Lange
    Developmental Biology Unit, UCL Institute of Child Health, London WC1N 1EH, UK
    Dev Biol 355:205-14. 2011
    ..Altogether, our findings identify PADs and deimination as developmentally regulated modulators of secondary injury response, and suggest that PADs might be valuable therapeutic targets for spinal cord injury...
  52. ncbi Novel enzyme activities and functional plasticity revealed by recombining highly homologous enzymes
    S Raillard
    Maxygen, Inc, Redwood City, CA 94063, USA
    Chem Biol 8:891-8. 2001
    ..We have shuffled two highly homologous triazine hydrolases and conducted an exploration of the substrate specificities of the resulting enzymes to acquire a better ..
  53. ncbi Arginine deiminase enhances dexamethasone-induced cytotoxicity in human T-lymphoblastic leukemia CCRF-CEM cells
    Eun Joo Noh
    Department of Pharmacology and BK21 Program for Medical Sciences, College of Medicine, Korea University, Seoul, Korea
    Int J Cancer 112:502-8. 2004
    ..These results suggest that ADI efficiently increases the anti-cancer effect of DEX on human leukemic CEM cells through G1 cell cycle arrest involving downregulation of c-myc and upregulation of p27Kip1...
  54. pmc The gene cluster for agmatine catabolism of Enterococcus faecalis: study of recombinant putrescine transcarbamylase and agmatine deiminase and a snapshot of agmatine deiminase catalyzing its reaction
    José L Llácer
    Instituto de Biomedicina de Valencia IBV CSIC, C Jaime Roig 11, 46010 Valencia, Spain
    J Bacteriol 189:1254-65. 2007
    ..A three-tongued agmatine-triggered gating opens or blocks access to the active center...
  55. pmc Genome-wide analysis reveals PADI4 cooperates with Elk-1 to activate c-Fos expression in breast cancer cells
    Xuesen Zhang
    Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
    PLoS Genet 7:e1002112. 2011
    ..These results define a novel role for PADI4 as a transcription factor co-activator...
  56. pmc Isolation and molecular analysis of the gene cluster for the arginine deiminase system from Streptococcus gordonii DL1
    Yiqian Dong
    Department of Oral Biology, University of Florida, Gainesville, Florida 32610, USA
    Appl Environ Microbiol 68:5549-53. 2002
    ..Thus, ArcR is a transcriptional activator that is required for induction and optimal expression of the S. gordonii ADS gene cluster...
  57. ncbi Kinetic characterization of protein arginine deiminase 4: a transcriptional corepressor implicated in the onset and progression of rheumatoid arthritis
    Patricia L Kearney
    Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, USA
    Biochemistry 44:10570-82. 2005
    ..Collectively, the studies described herein will provide a firm foundation for the future development of PAD4 selective inhibitors...
  58. pmc Protein arginine deiminase 4: evidence for a reverse protonation mechanism
    Bryan Knuckley
    Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, South Carolina 29208, USA
    Biochemistry 46:6578-87. 2007
    ..The results indicate that Cys645, the active site nucleophile, exists as the thiolate in the active form of the free enzyme. pH studies on PAD4 further suggest that this enzyme utilizes a reverse protonation mechanism...
  59. ncbi A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae
    Philippe DeNoel
    GlaxoSmithKline Biologicals, Rixensart, Belgium
    Vaccine 29:5495-501. 2011
    ..In conclusion, AS02-adjuvanted PhtD-dPly vaccine protects against S. pneumoniae-induced pneumonia. It is probable that the protection is at least partially mediated by PhtD- and Ply-specific antibodies...
  60. pmc Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor α target gene activation
    Xuesen Zhang
    Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
    Proc Natl Acad Sci U S A 109:13331-6. 2012
    ..Collectively, our data suggest that E2 stimulation induces the recruitment of PAD2 to target promoters by ERα, whereby PAD2 then citrullinates H3R26, which leads to local chromatin decondensation and transcriptional activation...
  61. ncbi Deimination of arginine residues in nucleophosmin/B23 and histones in HL-60 granulocytes
    Teruki Hagiwara
    Graduate School of Integrated Science, Yokohama City University, 22 2, Seto, Kanazawa Ku, Yokohama, 236 0027, Japan
    Biochem Biophys Res Commun 290:979-83. 2002
    ..The citrulline content of histones amounted to about 10% of the histone molecules. We discuss the implications of deimination of these proteins for their nuclear functions...
  62. ncbi Bacterial degradation of xenobiotic compounds: evolution and distribution of novel enzyme activities
    Dick B Janssen
    Biochemical Laboratory, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
    Environ Microbiol 7:1868-82. 2005
    ....
  63. pmc Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages
    E R Vossenaar
    Department of Biochemistry, University of Nijmegen, Nijmegen, The Netherlands
    Ann Rheum Dis 63:373-81. 2004
    ..Peptidylcitrulline can be generated by post-translational conversion of arginine residues. This process, citrullination, is catalysed by a group of calcium dependent peptidylarginine deiminase (PAD) enzymes...
  64. ncbi A new class of phosphotransferases phosphorylated on an aspartate residue in an amino-terminal DXDX(T/V) motif
    J F Collet
    Laboratory of Physiological Chemistry, Christian de Duve Institute of Cellular Pathology and Catholic University of Louvain, B 1200 Brussels, Belgium
    J Biol Chem 273:14107-12. 1998
    ..In conclusion, phosphomannomutase and L-3-phosphoserine phosphatase belong to a new phosphotransferase family with an amino-terminal DXDX(T/V) motif that serves as an intermediate phosphoryl acceptor...
  65. pmc Arginine deprivation, autophagy, apoptosis (AAA) for the treatment of melanoma
    N Savaraj
    VA Medical Center, Miami, FL 33125, USA
    Curr Mol Med 10:405-12. 2010
    ....
  66. ncbi Regulation of histone methylation by demethylimination and demethylation
    Robert J Klose
    Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    Nat Rev Mol Cell Biol 8:307-18. 2007
    ..Here, we examine the enzymatic and structural basis for the mechanisms that these enzymes use to counteract histone methylation and provide insights into their substrate specificity and biological function...
  67. pmc Three Bacillus cereus bacteriophage endolysins are unrelated but reveal high homology to cell wall hydrolases from different bacilli
    M J Loessner
    Institut fur Mikrobiologie, Forschungszentrum fur Milch und Lebensmittel Weihenstephan, Technische Universitat Munchen, Freising, Germany
    J Bacteriol 179:2845-51. 1997
    ..We speculate that the close relationship of the phage enzymes and cell wall autolysins is based upon horizontal gene transfer among different Bacillus phages and their hosts...
  68. ncbi Histone deimination antagonizes arginine methylation
    Graeme L Cuthbert
    Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom
    Cell 118:545-53. 2004
    ..The recruitment of PADI4 coincides with deimination of the histone H3 N-terminal tail. These results define deimination as a novel mechanism for antagonizing the transcriptional induction mediated by arginine methylation...
  69. pmc A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients
    T S Yang
    Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan 33305, Taiwan
    Br J Cancer 103:954-60. 2010
    ..This study aims to investigate the efficacy and pharmacodynamics of pegylated arginine deiminase (ADI-PEG 20), a systemic arginine deprivation agent, in Asian HCC patients...
  70. pmc Functional connection between deimination and deacetylation of histones
    Hélène Denis
    Free University of Brussels, Faculty of Medicine, Laboratory of Cancer Epigenetics, Brussels, Belgium
    Mol Cell Biol 29:4982-93. 2009
    ..These findings further substantiate the "transcriptional clock" concept, highlighting the dynamic connection between deimination and deacetylation of histones...
  71. ncbi Human PAD4 regulates histone arginine methylation levels via demethylimination
    Yanming Wang
    Department of Genetic Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Science 306:279-83. 2004
    ..Moreover, PAD4 activity is linked with the transcriptional regulation of estrogen-responsive genes in MCF-7 cells. These data suggest that PAD4 mediates gene expression by regulating Arg methylation and citrullination in histones...
  72. ncbi Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation via arginine deiminase
    Cheol Yong Yoon
    Department of Urology, College of Medicine, Korea University, Seoul 136 705, Korea
    Int J Cancer 120:897-905. 2007
    ..Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of RCC in ways of inhibitions of arginine availability and neovascularization...
  73. pmc Structural basis for histone N-terminal recognition by human peptidylarginine deiminase 4
    Kyouhei Arita
    Field of Supramolecular Biology, International Graduate School of Arts and Sciences, Yokohama City University, 1 7 29 Suehiro cho, Tsurumi ku, Yokohama 230 0045, Japan
    Proc Natl Acad Sci U S A 103:5291-6. 2006
    ..These observations provide structural insights into target protein recognition by histone modification enzymes and illustrate how PAD4 can target multiple arginine sites in the histone N-terminal tails...
  74. pmc nag genes of Ralstonia (formerly Pseudomonas) sp. strain U2 encoding enzymes for gentisate catabolism
    N Y Zhou
    School of Biological Sciences, University of Wales, Bangor, Gwynedd LL57 2UW, Wales, United Kingdom
    J Bacteriol 183:700-8. 2001
    ..NagJ is homologous to a glutathione S-transferase, and NagM and NagN are proteins homologous to each other and to other proteins of unknown function. Downstream of the operon is a partial sequence with homology to a transposase...
  75. pmc Autocitrullination of human peptidyl arginine deiminase type 4 regulates protein citrullination during cell activation
    Felipe Andrade
    Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA
    Arthritis Rheum 62:1630-40. 2010
    ..To address mechanisms that control the activity of human peptidyl arginine deiminase type 4 (PAD-4)...
  76. ncbi Contribution of myelin autoantigen citrullination to T cell autoaggression in the central nervous system
    Antonio Carrillo-Vico
    Centre for Inflammation Research, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
    J Immunol 184:2839-46. 2010
    ..The PAD2 and PAD4 enzymes were markedly upregulated in the inflamed CNS. Therefore, once inflammation is established, citrullination of target autoantigens can allow an expanded repertoire of T cells to contribute to CNS pathology...
  77. pmc Regulation and physiologic significance of the agmatine deiminase system of Streptococcus mutans UA159
    Ann R Griswold
    Department of Oral Biology, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610 0424, USA
    J Bacteriol 188:834-41. 2006
    ..The capacity to detoxify and catabolize agmatine is likely to have major ramifications on oral biofilm ecology...
  78. pmc Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases
    Charles Brenner
    Structural Biology and Bioinformatics Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Biochemistry 41:9003-14. 2002
    ..a motif related to the sequence HphiHphiHphiphi (phi, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides, and contain a approximately 30 kDa domain ..
  79. ncbi Genetics of rheumatoid arthritis: underlying evidence of ethnic differences
    Yuta Kochi
    University of Tokyo Hospital, Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan
    J Autoimmun 32:158-62. 2009
    ....
  80. ncbi Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase
    Tawnya L Bowles
    Department of Surgery, University of California, Davis Medical Center, Sacramento, CA 95817, USA
    Int J Cancer 123:1950-5. 2008
    ..Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of pancreatic cancer, a malignancy in which new therapy is desperately needed...
  81. pmc Arginine deiminase has multiple regulatory roles in the biology of Giardia lamblia
    Maria Carolina Touz
    Instituto de Investigacion Medica Mercedes y Martin Ferreyra, INIMEC CONICET, Friuli 2434, Cordoba, Argentina
    J Cell Sci 121:2930-8. 2008
    ..ADI is also sumoylated, which might modulate its activity. Our findings reveal a dual role played by ADI and define novel regulatory pathways used by Giardia for survival...
  82. ncbi Localization of peptidylarginine deiminase 4 (PADI4) and citrullinated protein in synovial tissue of rheumatoid arthritis
    X Chang
    Laboratory for Rheumatic Diseases, SNP Research Center, Institute of Physical and Chemical Research RIKEN, 1 7 22 Suehiro, Tsurumi ku, Yokohama, Kanagawa 230 0045, Japan
    Rheumatology (Oxford) 44:40-50. 2005
    ..Here, we localized the expression of PADI4 and the citrullinated protein product in synovial RA tissue...
  83. pmc Markers of fitness in a successful enzyme superfamily
    Karen N Allen
    Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, MA 02215 2521, USA
    Curr Opin Struct Biol 19:658-65. 2009
    ....
  84. ncbi Regulation of protein Citrullination through p53/PADI4 network in DNA damage response
    Chizu Tanikawa
    Laboratory of Molecular Medicine, Human Genome Center, Division of Gene Expression and Regulation, Institute of Medical Science, The University of Tokyo, Japan
    Cancer Res 69:8761-9. 2009
    ..of PADI4 inhibited tumor cell growth, and concordantly, the knockdown of PADI4 attenuated p53-mediated growth-inhibitory activity, demonstrating the significance of PADI4-mediated protein citrullination in the p53 signaling pathway..
  85. pmc Multiple two-component systems of Streptococcus mutans regulate agmatine deiminase gene expression and stress tolerance
    Yaling Liu
    Department of Oral Biology, University of Florida, Gainesville, FL 32610, USA
    J Bacteriol 191:7363-6. 2009
    ..We show here that the VicRK, ComDE, and CiaRH two-component systems influence AgDS gene expression in response to acidic and thermal stresses...
  86. pmc Resistance to arginine deiminase treatment in melanoma cells is associated with induced argininosuccinate synthetase expression involving c-Myc/HIF-1alpha/Sp4
    Wen Bin Tsai
    Department of Molecular Pathology, Unit 951, The University of Texas M D Anderson Cancer Center, 7435 Fannin Street, Houston, Texas 77030, USA
    Mol Cancer Ther 8:3223-33. 2009
    ..Inability of AS induction in A375 cells under arginine depletion conditions was correlated by the failure of c-Myc to interact with the AS promoter...
  87. pmc Environmental and growth phase regulation of the Streptococcus gordonii arginine deiminase genes
    Yaling Liu
    Department of Oral Biology, University of Florida, P O Box 100424, Gainesville, FL 32610 0424, USA
    Appl Environ Microbiol 74:5023-30. 2008
    ..gordonii was found...
  88. ncbi Poly(ethylene glycol) (PEG) conjugated arginine deiminase: effects of PEG formulations on its pharmacological properties
    Frederick W Holtsberg
    Department of Biology, T H Morgan Building, University of Kentucky, Lexington, KY 40506, USA
    J Control Release 80:259-71. 2002
    ..These data suggest that formulation of ADI with PEG of 20,000 mw results is the optimal method for formulating this promising therapeutic agent...
  89. ncbi High variability of peptidylarginine deiminase 4 (PADI4) in a healthy white population: characterization of six new variants of PADI4 exons 2-4 by a novel haplotype-specific sequencing-based approach
    Berthold Hoppe
    Institute of Transfusion Medicine, Campus Virchow Klinikum, Charite, Universitatsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
    J Mol Med (Berl) 82:762-7. 2004
    ..Further studies on disease association of PADI4 should be performed by haplotype-specific sequencing-based approaches to identify the exact genotype of the PADI4 fragment of interest...
  90. ncbi Proteomic analysis of lysosomal acid hydrolases secreted by osteoclasts: implications for lytic enzyme transport and bone metabolism
    Cornelia Czupalla
    Technical University of Dresden, 01307 Dresden, Germany
    Mol Cell Proteomics 5:134-43. 2006
    Osteoclasts, the bone-digesting cells, are polarized cells that secrete acid hydrolases into a resorption lacuna where bone degradation takes place. The molecular mechanisms underlying this process are poorly understood...
  91. ncbi Serum IgG antibodies to peptidylarginine deiminase 4 in rheumatoid arthritis and associations with disease severity
    E H Halvorsen
    Institute of Immunology, University of Oslo, Rikshospitalet University Hospital, 0027 Oslo, Norway
    Ann Rheum Dis 67:414-7. 2008
    ..Critical enzymes are often targeted by disease-specific antibodies in complex immune-mediated diseases. Here, we have tested for autoantibodies against human recombinant PAD4 (hPAD4) in Caucasian RA patients...
  92. ncbi Arginine deiminase, a potential anti-tumor drug
    Ye Ni
    Laboratory of Biocatalysis, School of Biotechnology, Jiangnan University, The Key Laboratory of Industrial Biotechnology, Ministry of Education, 1800 Lihu Road, Wuxi 214122, PR China
    Cancer Lett 261:1-11. 2008
    ..Discussions on heterogeneous expression of ADI, directed evolution for improving enzymatic properties, and HSA-fusion for increased in vivo activity conclude this review...
  93. ncbi Distribution of the ACME-arcA gene among methicillin-resistant Staphylococcus aureus from England and Wales
    Matthew J Ellington
    Staphylococcus Reference Laboratory SRL, Laboratory of HealthCare Associated Infection, Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London NW9 5EQ, UK
    J Antimicrob Chemother 61:73-7. 2008
    ..The arc gene cluster within the ACME may function as a virulence or strain survival factor. We determined the distribution of the ACME-associated arcA gene among genetically diverse MRSA from around England and Wales...
  94. ncbi Heterologous expression of glycosyl hydrolases in planta: a new departure for biofuels
    Larry E Taylor
    Chemical and Biosciences Center, National Renewable Energy Laboratory, 1617 Cole Blvd, Golden, CO 80401, USA
    Trends Biotechnol 26:413-24. 2008
    ..the improvement of biomass production and conversion characteristics to the heterologous production of glycosyl hydrolases in a high yielding bioenergy crop, holds considerable promise for improving the lignocellulosic conversion of ..
  95. pmc Inhibition of peptidyl-arginine deiminases reverses protein-hypercitrullination and disease in mouse models of multiple sclerosis
    Mario A Moscarello
    Molecular Structure and Function, The Research Institute, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
    Dis Model Mech 6:467-78. 2013
    ..2CA essentially prevented disease when administered before disease onset or before autoimmune induction, making hypercitrullination, and specifically PAD enzymes, a therapeutic target in MS models and thus possibly in MS...
  96. pmc Gene expression profiling identifies genes predictive of oral squamous cell carcinoma
    Chu Chen
    Program in Epidemiology, Fred Hutchinson Cancer Research Center, Department of Epidemiology, 1100 Fairview Avenue North, M5 C800 P O Box 19024, Seattle, WA 98109 1024, USA
    Cancer Epidemiol Biomarkers Prev 17:2152-62. 2008
    ..If confirmed in larger studies, the proposed models may hold promise for monitoring local recurrence at surgical margins and the development of second primary oral cancer in patients with OSCC...
  97. pmc Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune response in rheumatoid arthritis?
    Pamela Mangat
    The Kennedy Institute of Rheumatology Division, Imperial College, 65 Aspenlea Road, London, W6 8LH, UK
    Arthritis Res Ther 12:209. 2010
    ..Blockades of bacterial and human PADs may act as powerful novel therapies by inhibiting the generation of the antigens that trigger and sustain autoimmunity in rheumatoid arthritis...
  98. pmc Most efficient cocaine hydrolase designed by virtual screening of transition states
    Fang Zheng
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, Kentucky 40536, USA
    J Am Chem Soc 130:12148-55. 2008
    ....
  99. pmc Citrullination of inhibitor of growth 4 (ING4) by peptidylarginine deminase 4 (PAD4) disrupts the interaction between ING4 and p53
    Qin Guo
    Division of Medicinal Chemistry, College of Pharmacy, University of Texas, Austin, Texas 78712, USA
    J Biol Chem 286:17069-78. 2011
    ..These findings elucidate an interaction between posttranslational citrullination, acetylation, and methylation and highlight an unusual mechanism whereby citrullination of a non-histone protein impacts gene regulation...
  100. ncbi Directed evolution strategies for enantiocomplementary haloalkane dehalogenases: from chemical waste to enantiopure building blocks
    Jan G E van Leeuwen
    Biotransformation and Biocatalysis, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands
    Chembiochem 13:137-48. 2012
    ....
  101. ncbi Three types of mouse peptidylarginine deiminase: characterization and tissue distribution
    H Terakawa
    Laboratory of Biochemistry, Faculty of Agriculture, Ibaraki University
    J Biochem 110:661-6. 1991
    ..Western blot analysis showed that antibodies against the type II enzyme were immuno-crossreactive to the type III enzyme...

Research Grants63

  1. A Soft Topical Antiandrogenic Drug
    Wei Chu Xu; Fiscal Year: 2013
    ..or in development, (S)-HYG-440 was designed to avoid systemic activity by taking advantage of esterases and hydrolases found in most tissues in the body for metabolic deactivation, i.e. as a metabolically "soft" drug...
  2. Disease-related defects in dendritic cell processing of bacterial antigens
    Michael S Marks; Fiscal Year: 2012
    ..an ordered series of membrane fusion and fission events, leading to acidification, consequent activation of hydrolases, and synthesis of reactive oxygen and nitrogen species...
  3. CYTOSKELETAL REGULATION OF VESICLE TRANSPORT IN LIVER
    MARK A MC NIVEN; Fiscal Year: 2013
    ..These include the transferrin receptors (TfRs), the epidermal growth factor receptor (EGFR), and lysosomal hydrolases used in their degradation...
  4. Mode of Action of Thiorcarlide in Mycobacterium Tuberculosis
    Mary Jackson; Fiscal Year: 2012
    ..The genome of M. tb potentially encodes seven proteins related to epoxide hydrolases, some of which appear to be involved in the introduction of functional groups in mycolic acids and to be ..
  5. GLYCOSPHINGOLIPID METABOLISM AND MENTAL RETARDATION
    Glyn Dawson; Fiscal Year: 2013
    ..mouse model (ASMase (-/-)) to further show how the two major SMases are co-regulated and the role of lysosomal hydrolases in the regulation of the Cer/S1P ratio...
  6. Targeting Adipocyte Lipases to Treat Pancreatic Cancer-Associated Cachexia
    Enrique Saez; Fiscal Year: 2013
    ..All enzymes known to be involved in adipocyte lipolysis (ATGL, HSL, MGLL) are serine hydrolases. Genetic ablation of adipose triglyceride lipase (ATGL) and to a lesser extent hormone sensitive lipase (HSL) ..
  7. Identification of serine hydrolases involved in Plasmodium host cell invasion
    Brooke Anderson-White; Fiscal Year: 2013
    ..The serine hydrolases are a large family of enzymes with highly reactive and covalently modifiable active sites making them attractive ..
  8. A Role for Melanoregulin in RPE-mediated Phagocytosis
    KATHLEEN B BOESZE BATTAGLIA; Fiscal Year: 2010
    ..advance our understanding of how lysosomal enzymes are trafficked and what effect the collective loss of several hydrolases has on RPE health...
  9. Peptidoglycan Biogenesis in Escherichia Coli
    Thomas G Bernhardt; Fiscal Year: 2013
    ..In related work, we discovered that the EnvC protein is likely to be an activator of the PG hydrolases (amidases) AmiA and AmiB that stimulates their activity to bring about daughter cell separation during ..
  10. The Role of Bovine Sperm Acrosomal Membrane-Matrix Complex in Fertilization
    Subir K Nagdas; Fiscal Year: 2013
    ..by applicant): The mammalian sperm acrosome is a membrane bounded organelle which contains a variety of hydrolases that are utilized to penetrate the egg investments...
  11. HYDROLYTIC ENZYMES IN THE METABOLISM OF TOXINS
    Bruce D Hammock; Fiscal Year: 2013
    ..A set of under-studied metabolic enzymes include the epoxide hydrolases in the ?/?-hydrolase fold family. These enzymes degrade epoxides by adding water...
  12. Apoptosis and Necrosis in Pancreatitis
    Anna S Gukovskaya; Fiscal Year: 2012
    ..The material within autolysosomes is degraded by hydrolases such as cathepsins. An example of physiologic autophagy is that triggered by starvation...
  13. Supramolecular Complexes That Mediate Pneumococcal PG Biosynthesis and Virulence
    Malcolm E Winkler; Fiscal Year: 2012
    ..Aim 4 will determine how PG hydrolases modulate the supply of PG pentapeptide substrates used by PBPs and whether PG peptides play roles in organizing ..
  14. Membrane Remodeling and Protein Trafficking in Bacteria
    David Z Rudner; Fiscal Year: 2013
    ..2) Determine how membrane-tethered cell wall hydrolases and associated proteins govern membrane migration around the spore during engulfment...
  15. Regulation of Lung Inflammation by Catecholamines and Adrenergic Receptors
    Peter A Ward; Fiscal Year: 2013
    ..for the presence of a2 adrenergic receptors (a2A, a2B, a2C) as well as inducible catecholamine synthases and hydrolases, and how these receptors and enzymes affect cell responses to C5a, LPS, or both...
  16. STRUCTURAL ANALYSIS OF THE MANNOSE 6-PHOSPHATE RECEPTORS
    Nancy M Dahms; Fiscal Year: 2013
    ..dependent MPR (CD-MPR) play a key role in lysosome biogenesis by delivering ~60 different newly synthesized acid hydrolases to the lysosome by binding to mannose 6-phosphate (M6P) residues on their N-glycans...
  17. Identification and Therapeutic Valiation of Adipocyte Serine Hydrolases of Metab
    Enrique Saez; Fiscal Year: 2013
    ..Despite their importance in fat cell physiology, the majority of serine hydrolases have not been studied...
  18. Regulation of Substrate Binding and Catalysis in tRNase Z
    LOUIS F LEVINGER; Fiscal Year: 2010
    ..The endonuclease tRNase Z, a member of the -lactamase family of metal-dependent hydrolases, removes the 3'end trailer so that CCA can be added by tRNA nucleotidyltransferase...
  19. Elucidating Perforin-2 mediated killing mechanisms against pathogenic bacteria
    RYAN MICHAEL MCCORMACK; Fiscal Year: 2013
    ..bacterial killing mechanisms at this interface include reactive oxygen species (ROS), nitric oxide (NO), and hydrolases. Notwithstanding this body of knowledge, there is relatively little knowledge of exactly how these components ..
  20. Molecular characterization of endocannabinoid degradative enzymes
    JACQUELINE LORAYNE BLANKMAN; Fiscal Year: 2012
    ..hydrolase activity in mouse brain proteomes: monoacylglyceride lipase (MAGL), and the uncharacterized alpha/beta hydrolases 6 and 12 (ABHD6 and ABHD12)...
  21. FORESPORE ENGULFMENT DURING B SUBTILIS SPORULATION
    KIT J POGLIANO; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: Peptidoglycan hydrolases are found in all bacteria that synthesize peptidoglycan, and are potentially lethal because their activity must ..
  22. STRUCTURE, BIOSYNTHESIS &FUNCTION OF GLYCOPROTEINS
    Stuart A Kornfeld; Fiscal Year: 2013
    ..understanding of the phosphomannosyl targeting system which functions in the delivery of newly synthesized acid hydrolases to lysosomes...
  23. Structure-Function Studies of Endocannabinoid Biosynthetic Enzymes
    JOSE OLUCHA - ALVAREZ; Fiscal Year: 2013
    ..the structure and biochemistry of these key ECS enzymes, the only known four helical pass transmembrane serine hydrolases in mammals...
  24. The Comprehensive Center for Chemical Probe Discovery and Optimization at Scripps
    Hugh Rosen; Fiscal Year: 2013
    ..Target classes screened by the core include receptors, transcription factors, transferases, hydrolases, oxidoreductases, lyases, isomerases and ligases;protein interactions (protein-protein, protein-DNA, and protein-..
  25. Biogenesis and Function of Guide RNAs
    RUSLAN AFASIZHEV; Fiscal Year: 2012
    ..In preliminary studies we identified GRBC1/2-associated proteins, including NUDIX hydrolases, DExD/H RNA helicases, RNA binding proteins, and polypeptides lacking identifiable domains...
  26. FUNCTIONAL/STRUCTURAL STUDIES OF MAMMALIAN NEURAMINIDASE
    ALESSANDRA D AZZO; Fiscal Year: 2009
    ..include cytosolic, lysosomal, and plasma membrane isoforms, and clues about the physiologic roles of these hydrolases, in particular NEU1, have emerged only recently...
  27. Lysosomal Damage, Impaired Autophagy, and Alcoholic Pancreatitis
    Olga A Mareninova; Fiscal Year: 2013
    ..dysfunction a prominent manifestation of which is defective processing/maturation of cathepsins, major lysosomal hydrolases. Further, our findings revealed that impaired autophagy mediates 2 key pathologic responses of pancreatitis: ..
  28. Mechanism of Activation of Probiotic Bifidobacteria by Prebiotic Milk Glycans
    Carolyn Slupsky; Fiscal Year: 2013
    ..2. To completely characterize the bifidobacterial transporters and glycosyl hydrolases necessary to deconstruct these complex milk oligosaccharides. 3...
  29. Lipidomic mapping of the cellular anatomy of brain endocannabinoid metabolism
    Andreu Viader; Fiscal Year: 2013
    ..will use targeted and untargeted lipidomic profiling to examine the compartmentalization of the major brain 2-AG hydrolases (MAGL, ABHD6 and ABHD12) in neurons vs...
  30. Remodeling of the M. tuberculosis cell wall by the host microenvironment
    Jordi B Torrelles; Fiscal Year: 2010
    ..e., surfactant). Each of these alveolar compartment cells contains its own unique array of hydrolases that are released to the alveolar environment and sequestered in surfactant. When M...
  31. Function of human lung mucosal hydrolases during M. tuberculosis infection
    Jordi B Torrelles; Fiscal Year: 2013
    ..a dynamic phase where it encounters pulmonary surfactant that contains homeostatic and antimicrobial enzymes (hydrolases) which alter the M. tb cell wall. These hydrolases release biologically active M...
  32. Chemoproteomic methods for serine hydrolase inhibitor development
    Benjamin F Cravatt; Fiscal Year: 2013
    ..to develop potent, selective, and in vivo-active inhibitors for a substantial fraction of mammalian serine hydrolases (SHs), which are a large and diverse enzyme class that represent ~1% of all human proteins...
  33. ACTIVITY-BASED KINASE DISCOVERY IN SMALL CELL LUNG CANCER
    Eric B Haura; Fiscal Year: 2013
    ..Using ABPP, a number of enzyme families have been studied, including serine hydrolases, kinases, phosphatases, and metalloproteinases...
  34. Endocannabinoid Metabolic Enzymes: Structure, Function, In Vivo Inhibition
    Benjamin F Cravatt; Fiscal Year: 2013
    ..Key outstanding questions include: 1) what are the mechanisms and three-dimensional structures of EC hydrolases? 2) what are the neurochemical and physiological consequences of perturbing the function of EC hydrolases in ..
  35. Restoration of alveolar macrophage function in HIV patients: A clinical study.
    David G Russell; Fiscal Year: 2013
    ..e. phagosome acidification, the acquisition of lysosomal hydrolases, the generation of reactive oxygen and nitrogen intermediates, and the capacity of the HIV-infected cells to ..
  36. Biochemical Characterization of Specificity for Family 3 Glycoside Hydrolases
    Dylan Dodd; Fiscal Year: 2013
    ..Glycoside hydrolases (GHs) comprise a significant proportion of the genes encoded by microbial genomes within the human distal gut ..
  37. Long-lasting cocaine-metabolizing enzyme for cocaine addiction treatment
    Chang Guo Zhan; Fiscal Year: 2013
    ..5 [unreadable]M). Nevertheless, we have recently designed and discovered a set of BChE mutants, known as cocaine hydrolases (CocHs), with >1,000-fold improved catalytic efficiency against (-)-cocaine compared to wild-type BChE...
  38. Identification of novel therapeutic approaches for TETS and OP intoxication
    Michael A Rogawski; Fiscal Year: 2011
    ..research project is to test the hypothesis that AMPA receptor antagonists and/or inhibitors of soluble epoxide hydrolases will significantly improve outcome following exposure to acutely toxic levels of TETS and parathion by extending ..
  39. Analysis of Required Proteins for Engulfment during Bacillus subtilis Sporulation
    RACHELLE MARIE TRIAL; Fiscal Year: 2011
    ..Engulfment offers an ideal system for understanding how cell wall hydrolases are spatially and temporally regulated, and how they contribute to this dynamic process...
  40. Novel Organophosphorous Hydrolases for Decontamination
    Andrew Mesecar; Fiscal Year: 2007
    ..Enzymes known as phosphotriesterases, commonly called organophosphorous hydrolases (OPH), are capable of hydrolyzing OP and CW agents into harmless products...
  41. Discovery of Natural Product based Drugs and Bioenergetic Materials from CR
    David H Sherman; Fiscal Year: 2013
    ..g., thioester hydrolases and decarboxylases) with application in liquid fuel production (biodiesel).
  42. ACROSOMAL ENZYMES AND THEIR ROLE IN FERTILIZATION
    PRAKASH SRIVASTAVA; Fiscal Year: 1993
    ..action of binding to the zona and its subsequent penetration may involve a sequential action of acrosomal hydrolases bound to IAM...
  43. AUTOPHAGY IN GLIA AND NEURONS
    William Dunn; Fiscal Year: 1993
    ..In addition to undegraded proteins, these structures contain lysosomal acid hydrolases, dolichyl oligosaccharides normally found in rough endoplasmic reticulum (RER), and the c-subunit of the ..
  44. Quantitative chemical proteomics of dynamic palmitoylation in cells
    BRENT RANDALL MARTIN; Fiscal Year: 2010
    ..we have identified a novel protein thioesterase, and plan to expand this assay to other uncharacterized hydrolases. We plan to further characterize the relationship between APT1 and cancer by proteomic identification of ..
  45. MOLECULAR BASIS OF FAMILIAL STUTTERING
    Stuart A Kornfeld; Fiscal Year: 2012
    ..three genes that encode the two enzymes that add a Mannose 6-phosphate tag onto newly synthesized lysosomal acid hydrolases. This tag serves to direct ("target") the acid hydrolases to lysosomes...
  46. Development of a Cocaine-Metabolizing Enzyme for Drug Overdose Treatment
    Chang Guo Zhan; Fiscal Year: 2013
    ..computational-experimental effort has led to discovery of high-activity mutants of human BChE, known as cocaine hydrolases (CocHs), with >1,000-fold improved catalytic efficiency against cocaine compared to wild-type BChE...
  47. Data Mining Assisted Discovery of Novel Organophosphorou
    Robert Turner; Fiscal Year: 2005
    ..Enzymes known as phosphotriesterases, commonly called organo-phosphate hydrolases (OPH's), are capable of hydrolyzing OP pesticides and CW agents into harmless products...
  48. HYDROLYTIC ENZYMES IN THE METABOLISM OF TOXINS
    Bruce Hammock; Fiscal Year: 2007
    ..This proposal targets two enzyme classes, epoxide hydrolases (EHs) and esterases, which are both members of the alpha/beta-hydrolase fold family...
  49. Quantitative chemical proteomics of dynamic palmitoylation in cells
    BRENT RANDALL MARTIN; Fiscal Year: 2013
    ..we have identified a novel protein thioesterase, and plan to expand this assay to other uncharacterized hydrolases. We plan to further characterize the relationship between APT1 and cancer by proteomic identification of ..
  50. Novel Organophosphorous Hydrolases for Decontamination
    Andrew Mesecar; Fiscal Year: 2004
    ..Enzymes known as phosphotriesterases, commonly called organophosphorous hydrolases (OPH), are capable of hydrolyzing OP and CW agents into harmless products...
  51. SBIR TOPIC321:CHEMICALLY DEFINED GLYCAN LIBRARIES FOR REFERENCE STANDARDS AND GLY
    Baolin Wu; Fiscal Year: 2013
    ..This process involves several well characterized glycosyltransferases, glycoside hydrolases and other enzymes. All the N-glycans will be purified to 98%, and fully characterized by NMR and MS...
  52. AdoHcy Hydrolase Inhibitors as Antiparasitic Agents
    RONALD BORCHARDT; Fiscal Year: 2006
    ..These results suggest that, if specific inhibitors of parasite AdoHcy hydrolases could be designed, they would have clinical potential as antiparasitic agents...
  53. STRUCTURE AND MECHANISMS OF FAMILY 18 CHITINASES
    JEFFRY MADURA; Fiscal Year: 2002
    ..will elucidate the biochemistry and structural biology for a class of enzymes and proteins known as glycosyl hydrolases. We will specifically study glycosyl hydrolases that hydrolyze chitin and chitin- like polymers into smaller ..
  54. CYTOCHROME P450 DEPENDENT ARACHIDONIC ACID METABOLISM
    Deanna Kroetz; Fiscal Year: 2004
    ..The EETs are further metabolized by epoxide hydrolases to the corresponding dihydroxyeicosatrienoic acids (DHETs)...
  55. BIOCHEMICAL TOXICOLOGY OF CARBOXYESTERASES
    Andrew Parkinson; Fiscal Year: 1992
    ..the project are (1) to purify from rat liver microsomes the three major constitutive forms of carboxyesterase (hydrolases A, B and C) and the major phenobarbital-inducible form of carboxyesterase (hydrolase D), and (2) to characterize ..
  56. High Throughput Bioengineering of Detoxification Enzymes
    Margaret Bradley; Fiscal Year: 2003
    Our revised project High Throughput Bioengineering of Detoxification Enzymes focuses on organophosphate hydrolases, which have immediate value for mediation or detection of chemical warfare agents (CW; i.e...
  57. MORPHOGENESIS OF THE MUREIN SACCULUS OF ESCHERICHIA COLI
    Michael Hochberg; Fiscal Year: 1990
    ..In this region both the murein polymerases and murein hydrolases are most active...
  58. ENTEROKINASE--AN INTESTINAL DIGESTIVE PROTEASE
    J Sadler; Fiscal Year: 2003
    ..This regulatory mechanism confines the activity of digestive hydrolases to the gut...
  59. INTESTINAL PEPTIDE HYDROLASES AND PEPTIDE TRANSPORT
    Young Kim; Fiscal Year: 2000
    ..Cellular changes in the expression of ACE and DPPIV along the crypt-villus axis during intestinal adaptation will be monitored by in situ hybridization and immunohistochemistry. ..
  60. HYDROLYSIS OF VITAMIN A ESTERS IN LIVER
    EARL HARRISON; Fiscal Year: 2007
    ..Neutral and acid retinyl ester hydrolases (REHs) have been purified from rat liver and shown by sequence analysis to be carboxylesterases, ES-2 and ES-10...
  61. REGULATION OF ALPHA-L-FUCOSIDASE IN HEALTH AND DISEASE
    RICHARD DI CIOCCIO; Fiscal Year: 1993
    The accurate delivery of newly synthesized and hydrolases from the rough endoplasmic reticulum to residency in lysosomes or extracellular fluids involves a series of co- and post-translational modifications of the protein and carbohydrate ..
  62. Structure, Function and Mechanism of Nudix Hydrolases
    L Amzel; Fiscal Year: 2006
    ..The Nudix family of hydrolases can be divided into families based on their substrate specificity, catalytic activity and phenotype...
  63. STUDY OF SAPOSINS' BIOLOGICAL FUNCTIONS
    Xiaoyang Qi; Fiscal Year: 2003
    ..These saposins or activator proteins are essential for normal function of several hydrolases involved in the glycosphingolipid/sphingolipid (GSL/JSL) catabolism pathway in lysosomes...