substrate specificity


Summary: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

Top Publications

  1. pmc REBASE--a database for DNA restriction and modification: enzymes, genes and genomes
    Richard J Roberts
    New England Biolabs, Inc, 240 County Road, Ipswich, MA 01938, USA
    Nucleic Acids Res 38:D234-6. 2010
  2. pmc Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites
    Atanu Maiti
    Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Biol Chem 286:35334-8. 2011
  3. pmc One step at a time: endoplasmic reticulum-associated degradation
    Shruthi S Vembar
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Nat Rev Mol Cell Biol 9:944-57. 2008
  4. pmc Genome engineering with zinc-finger nucleases
    Dana Carroll
    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84112 5650, USA
    Genetics 188:773-82. 2011
  5. pmc Evolution, substrate specificity and subfamily classification of glycoside hydrolase family 5 (GH5)
    Henrik Aspeborg
    Division of Glycoscience, School of Biotechnology, KTH Royal Institute of Technology, AlbaNova University Center, Stockholm SE 106 91, Sweden
    BMC Evol Biol 12:186. 2012
  6. ncbi Mechanism of human SIRT1 activation by resveratrol
    Margie T Borra
    Department of Biomolecular Chemistry, University of Wisconsin Madison, Madison, Wisconsin 53706, USA
    J Biol Chem 280:17187-95. 2005
  7. ncbi Mammalian caspases: structure, activation, substrates, and functions during apoptosis
    W C Earnshaw
    Institute of Cell and Molecular Biology, University of Edinburgh, Scotland, United Kingdom
    Annu Rev Biochem 68:383-424. 1999
  8. ncbi The conformational plasticity of protein kinases
    Morgan Huse
    Department of Biological Sciences, Stanford University, Palo Alto, California 94305, USA
    Cell 109:275-82. 2002
  9. ncbi Strategies for MMP inhibition in cancer: innovations for the post-trial era
    Christopher Mark Overall
    Department of Oral Biological and Medical Sciences, C I H R Group in Matrix Dynamics, University of British Columbia, V6T 1Z3, Canada
    Nat Rev Cancer 2:657-72. 2002
  10. doi Identification of Holliday junction resolvases from humans and yeast
    Stephen C Y Ip
    Genetic Recombination Laboratory, Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
    Nature 456:357-61. 2008

Detail Information

Publications405 found, 100 shown here

  1. pmc REBASE--a database for DNA restriction and modification: enzymes, genes and genomes
    Richard J Roberts
    New England Biolabs, Inc, 240 County Road, Ipswich, MA 01938, USA
    Nucleic Acids Res 38:D234-6. 2010
    ..The contents of REBASE may be browsed from the web ( and selected compilations can be downloaded by ftp ( Additionally, monthly updates can be requested via email...
  2. pmc Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites
    Atanu Maiti
    Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Biol Chem 286:35334-8. 2011
  3. pmc One step at a time: endoplasmic reticulum-associated degradation
    Shruthi S Vembar
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Nat Rev Mol Cell Biol 9:944-57. 2008
    ..Here, we summarize our current understanding of each step during ERAD, with emphasis on the factors that catalyse distinct activities...
  4. pmc Genome engineering with zinc-finger nucleases
    Dana Carroll
    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84112 5650, USA
    Genetics 188:773-82. 2011
    ..The bright prospects for future applications of ZFNs, including human gene therapy, are discussed...
  5. pmc Evolution, substrate specificity and subfamily classification of glycoside hydrolase family 5 (GH5)
    Henrik Aspeborg
    Division of Glycoscience, School of Biotechnology, KTH Royal Institute of Technology, AlbaNova University Center, Stockholm SE 106 91, Sweden
    BMC Evol Biol 12:186. 2012
    ..With the objective of improving the differentiation of enzyme specificities in a knowledge-based context, and to obtain new evolutionary insights, we present here a new, robust subfamily classification of family GH5...
  6. ncbi Mechanism of human SIRT1 activation by resveratrol
    Margie T Borra
    Department of Biomolecular Chemistry, University of Wisconsin Madison, Madison, Wisconsin 53706, USA
    J Biol Chem 280:17187-95. 2005
    ..We propose that binding of resveratrol to SIRT1 promotes a conformational change that better accommodates the attached coumarin group...
  7. ncbi Mammalian caspases: structure, activation, substrates, and functions during apoptosis
    W C Earnshaw
    Institute of Cell and Molecular Biology, University of Edinburgh, Scotland, United Kingdom
    Annu Rev Biochem 68:383-424. 1999
    ..Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death...
  8. ncbi The conformational plasticity of protein kinases
    Morgan Huse
    Department of Biological Sciences, Stanford University, Palo Alto, California 94305, USA
    Cell 109:275-82. 2002
    ..By contrast, crystal structures of inactive kinases have revealed a remarkable plasticity in the kinase domain that allows the adoption of distinct conformations in response to interactions with specific regulatory domains or proteins...
  9. ncbi Strategies for MMP inhibition in cancer: innovations for the post-trial era
    Christopher Mark Overall
    Department of Oral Biological and Medical Sciences, C I H R Group in Matrix Dynamics, University of British Columbia, V6T 1Z3, Canada
    Nat Rev Cancer 2:657-72. 2002
    ..What are the different approaches that can be used to target MMPs, and which of these might lead to new therapeutic strategies for cancer?..
  10. doi Identification of Holliday junction resolvases from humans and yeast
    Stephen C Y Ip
    Genetic Recombination Laboratory, Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
    Nature 456:357-61. 2008
    ..Recombinant GEN1 and Yen1 resolve Holliday junctions by the introduction of symmetrically related cuts across the junction point, to produce nicked duplex products in which the nicks can be readily ligated...
  11. pmc LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1
    Jose M Lizcano
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, UK
    EMBO J 23:833-43. 2004
    ..Between them, these kinases may mediate the physiological effects of LKB1, including its tumour suppressor function...
  12. ncbi The anaphase promoting complex/cyclosome: a machine designed to destroy
    Jan Michael Peters
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Nat Rev Mol Cell Biol 7:644-56. 2006
    ..5-MDa complex. Recent discoveries have revealed an unexpected multitude of mechanisms that control APC/C activity, and have provided a first insight into how this unusual ubiquitin ligase recognizes its substrates...
  13. ncbi A "silent" polymorphism in the MDR1 gene changes substrate specificity
    Chava Kimchi-Sarfaty
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Science 315:525-8. 2007
  14. ncbi A genomic and functional inventory of deubiquitinating enzymes
    Sebastian M B Nijman
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cell 123:773-86. 2005
    ..In addition, we review the literature concerning these enzymes, with particular emphasis on their function, specificity, and the regulation of their activity...
  15. ncbi Serine protease mechanism and specificity
    Lizbeth Hedstrom
    Department of Biochemistry, MS 009, Brandeis University, Waltham, Massachusetts 02454, USA
    Chem Rev 102:4501-24. 2002
  16. ncbi The small GTP-binding protein rac regulates growth factor-induced membrane ruffling
    A J Ridley
    Institute for Cancer Research, Chester Beatty Laboratories, London, England
    Cell 70:401-10. 1992
    ..We propose that rac and rho are essential components of signal transduction pathways linking growth factors to the organization of polymerized actin...
  17. ncbi Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase
    Geng Wu
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 11:1445-56. 2003
  18. doi Targeting cancer with small molecule kinase inhibitors
    Jianming Zhang
    Dana Farber Cancer Institute, Department of Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 9:28-39. 2009
    ..This Review provides a broad overview of some of the approaches currently used to discover and characterize new kinase inhibitors...
  19. ncbi Histone demethylation mediated by the nuclear amine oxidase homolog LSD1
    Yujiang Shi
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Cell 119:941-53. 2004
    ..The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases...
  20. doi From promiscuity to precision: protein phosphatases get a makeover
    David M Virshup
    Program in Cancer and Stem Cell Biology, Duke NUS Graduate Medical School Singapore, Singapore, Republic of Singapore
    Mol Cell 33:537-45. 2009
    ..As recent publications illustrate, these regulatory subunits confer specificity, selectivity, localization, and regulation on these important enzymes...
  21. ncbi Substrate-specific activation of sirtuins by resveratrol
    Matt Kaeberlein
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 280:17038-45. 2005
    ..In light of these findings, the mechanism accounting for putative longevity effects of resveratrol should be reexamined...
  22. ncbi Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9
    M H Tatham
    Institute of Biomolecular Sciences, University of St Andrews, North Haugh, St Andrews KY16 5ST, United Kingdom
    J Biol Chem 276:35368-74. 2001
    ..The ability to form polymeric chains is not shared by SUMO-1, and although all SUMO species use the same conjugation machinery, modification by SUMO-1 and SUMO-2/-3 may have distinct functional consequences...
  23. pmc Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution
    Liam J Holt
    Departments of Physiology and Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
    Science 325:1682-6. 2009
    ..The gain or loss of phosphorylation sites in rapidly evolving regions could facilitate the evolution of kinase-signaling circuits...
  24. pmc Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation
    Anjanabha Saha
    Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Mol Cell 32:21-31. 2008
  25. pmc N-terminal acetylation of cellular proteins creates specific degradation signals
    Cheol Sang Hwang
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Science 327:973-7. 2010
    ..Several examined proteins of diverse functions contained these N-terminal degrons, termed AcN-degrons, which are a prevalent class of degradation signals in cellular proteins...
  26. pmc Computational reprogramming of homing endonuclease specificity at multiple adjacent base pairs
    Justin Ashworth
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Nucleic Acids Res 38:5601-8. 2010
  27. pmc RNA helicases at work: binding and rearranging
    Eckhard Jankowsky
    Center for RNA Molecular Biology and Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA
    Trends Biochem Sci 36:19-29. 2011
    ..This review outlines our current view on major structural and mechanistic themes of RNA helicase function, and on emerging physical models for cellular roles of these enzymes...
  28. ncbi MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis
    H Maki
    Department of Biochemistry, Faculty of Medicine, Kyushu University, Fukuoka, Japan
    Nature 355:273-5. 1992
    ..This indicates that elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis...
  29. ncbi One-thousand-and-one substrates of protein kinase CK2?
    Flavio Meggio
    Dipartimento di Chimica Biologica and Istituto di Neuroscienze del CNR, Università di Padova and Venetian Institute for Molecular Medicine VIMM, Padova, Italy
    FASEB J 17:349-68. 2003
    ..The possibility that CK2 phosphosites play some global role, e.g., by destabilizing alpha helices, counteracting caspase cleavage, and generating adhesive motifs, will be discussed...
  30. doi Enzyme promiscuity: a mechanistic and evolutionary perspective
    Olga Khersonsky
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Annu Rev Biochem 79:471-505. 2010
    ..Finally, we address the hypothesis that promiscuous enzymatic activities serve as evolutionary starting points and highlight the unique evolutionary features of promiscuous enzyme functions...
  31. pmc How do site-specific DNA-binding proteins find their targets?
    Stephen E Halford
    Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK
    Nucleic Acids Res 32:3040-52. 2004
    ..Finally, we discuss how single molecule techniques might be used to study the dynamics of DNA site-specific targeting of proteins...
  32. ncbi Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery
    Stephane Angers
    Howard Hughes Medical Institute, University of Washington, School of Medicine, Box 357280, Seattle, Washington 98195, USA
    Nature 443:590-3. 2006
    ..Together, our structural and proteomic results reveal the structural mechanisms and molecular logic underlying the assembly and versatility of a new family of cullin-RING E3 complexes...
  33. ncbi Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis
    Marcin Nowotny
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 121:1005-16. 2005
    ..In transposases, they are symmetrically coordinated and exchange roles to alternately activate a water and a 3'-OH for successive strand cleavage and transfer by a ping-pong mechanism...
  34. pmc Human flap endonuclease structures, DNA double-base flipping, and a unified understanding of the FEN1 superfamily
    Susan E Tsutakawa
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Cell 145:198-211. 2011
    ..conserved motifs bind and open dsDNA; direct the target region into the helical gateway, permitting only nonbase-paired oligonucleotides active site access; and support a unified understanding of superfamily substrate specificity.
  35. pmc Tapping natural reservoirs of homing endonucleases for targeted gene modification
    Ryo Takeuchi
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North A3 025, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 108:13077-82. 2011
    ..The ubiquitous presence and diversity of LHEs described in this study may facilitate the creation of many tailored nucleases for genome editing...
  36. doi Structural basis for the requirement of additional factors for MLL1 SET domain activity and recognition of epigenetic marks
    Stacey M Southall
    Institute of Cancer Research, Chester Beatty Laboratories, Chelsea, London, UK
    Mol Cell 33:181-91. 2009
  37. pmc Deciphering protein kinase specificity through large-scale analysis of yeast phosphorylation site motifs
    Janine Mok
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Sci Signal 3:ra12. 2010
    ..Together, these results elucidate how kinase catalytic domains recognize their phosphorylation targets and suggest general avenues for the identification of previously unknown kinase substrates across eukaryotes...
  38. ncbi MazF cleaves cellular mRNAs specifically at ACA to block protein synthesis in Escherichia coli
    Yonglong Zhang
    Department of Biochemistry, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA
    Mol Cell 12:913-23. 2003
    ..The role of such endoribonucleases may have broad implication in cell physiology under various growth conditions...
  39. ncbi Ubiquitin: structures, functions, mechanisms
    Cecile M Pickart
    Department of Biochemistry and Molecular Biology Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Biochim Biophys Acta 1695:55-72. 2004
    ..This article reviews the basic biochemistry of these protein conjugation reactions, focusing on ubiquitin itself and emphasizing recent insights into mechanism and specificity...
  40. pmc Ribonuclease H: the enzymes in eukaryotes
    Susana M Cerritelli
    Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    FEBS J 276:1494-505. 2009
    ..Mutations in any of the three subunits of human RNase H2 cause Aicardi-Goutières syndrome, a human neurological disorder with devastating consequences...
  41. ncbi SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity
    Estela Jacinto
    Department of Physiology and Biophysics, UMDNJ Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Cell 127:125-37. 2006
    ..Our findings reveal that the SIN1-rictor-mTOR function in Akt-Ser473 phosphorylation is required for TORC2 function in cell survival but is dispensable for TORC1 function...
  42. ncbi The calpain system
    Darrell E Goll
    Muscle Biology Group, University of Arizona, Tucson, AZ 85721, USA
    Physiol Rev 83:731-801. 2003
    ..Deregulated calpain activity following loss of Ca2+ homeostasis results in tissue damage in response to events such as myocardial infarcts, stroke, and brain trauma...
  43. ncbi Mus81-Eme1 are essential components of a Holliday junction resolvase
    M N Boddy
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 107:537-48. 2001
    ..The mus81 meiotic defect is rescued by expression of a bacterial Holliday junction resolvase. These findings constitute strong evidence that Mus81 and Eme1 are subunits of a nuclear Holliday junction resolvase...
  44. pmc Mechanism of Holliday junction resolution by the human GEN1 protein
    Ulrich Rass
    London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts, United Kingdom
    Genes Dev 24:1559-69. 2010
    ..However, the unique feature of GEN1 that distinguishes it from other Rad2/XPG nucleases is its ability to dimerize on HJs. This functional adaptation provides the two symmetrically aligned active sites required for HJ resolution...
  45. doi Dicer recognizes the 5' end of RNA for efficient and accurate processing
    Jong Eun Park
    School of Biological Sciences, Seoul National University, Seoul 151 742, Korea
    Nature 475:201-5. 2011
    ..Thus, 5'-end recognition by Dicer is important for precise and effective biogenesis of miRNAs. Insights from this study should also afford practical benefits to the design of small hairpin RNAs...
  46. pmc The 1.6 Å crystal structure of pyranose dehydrogenase from Agaricus meleagris rationalizes substrate specificity and reveals a flavin intermediate
    Tien Chye Tan
    School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden
    PLoS ONE 8:e53567. 2013
    ..of carbohydrates in the PDH active site allowed us to rationalize the previously reported patterns of substrate specificity and regioselectivity...
  47. ncbi A dynamic role of HAUSP in the p53-Mdm2 pathway
    Muyang Li
    Institute for Cancer Genetics and Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, NY 10032, USA
    Mol Cell 13:879-86. 2004
    ..This study provides an example of an ubiquitin ligase (Mdm2) that is directly regulated by a deubiquitinase (HAUSP) and also reveals a dynamic role of HAUSP in the p53-Mdm2 pathway...
  48. pmc ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions
    Philippe P Roux
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Microbiol Mol Biol Rev 68:320-44. 2004
    ..In this article, we review the existing data on the MKs and discuss their physiological functions based on recent discoveries...
  49. pmc Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays
    Avinash Persaud
    Programs in Cell Biology and Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada
    Mol Syst Biol 5:333. 2009
    ..relatives: Nedd4 (Nedd4-1) and Nedd4L (Nedd4-2), but their global substrate recognition or differences in substrate specificity are unknown...
  50. ncbi Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases
    Bing Hao
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 26:131-43. 2007
  51. ncbi Substrate specificities of caspase family proteases
    R V Talanian
    BASF Bioresearch Corp, Worcester, Massachusetts 01605, USA
    J Biol Chem 272:9677-82. 1997
    ..The results also suggest the design of optimal peptidic substrates and inhibitors...
  52. ncbi Chaperone release and unfolding of substrates in type III secretion
    Yukihiro Akeda
    Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Nature 437:911-5. 2005
    ..Our results show a similarity between the mechanisms of substrate recognition by type III protein secretion systems and AAA + ATPase disassembly machines...
  53. ncbi Identification and characterization of a cyclic di-GMP-specific phosphodiesterase and its allosteric control by GTP
    Matthias Christen
    Division of Molecular Microbiology, Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland
    J Biol Chem 280:30829-37. 2005
  54. doi Crystal structure of the FTO protein reveals basis for its substrate specificity
    Zhifu Han
    National Institute of Biological Sciences, No 7 Science Park Road, Beijing 102206, China
    Nature 464:1205-9. 2010
    ..Taken together, these results provide a structural basis for understanding FTO substrate-specificity, and serve as a foundation for the rational design of FTO inhibitors...
  55. ncbi Structure and functions of the GNAT superfamily of acetyltransferases
    Matthew W Vetting
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Arch Biochem Biophys 433:212-26. 2005
  56. doi An overview of mannan structure and mannan-degrading enzyme systems
    L R S Moreira
    Departamento de Biologia Celular, Laboratorio De Enzimologia, Universidade de Brasilia, CEP 70910 900 Brasilia, DF, Brazil
    Appl Microbiol Biotechnol 79:165-78. 2008
    ..Mannan-degrading enzymes have found applications in the pharmaceutical, food, feed, and pulp and paper industries. This review reports the structure of mannans and some biochemical properties and applications of mannan-degrading enzymes...
  57. doi Nucleotidyl cyclase activity of soluble guanylyl cyclase α1β1
    Kerstin Y Beste
    Institute of Pharmacology, Hannover Medical School, Hannover, Germany
    Biochemistry 51:194-204. 2012
    ..In conclusion, soluble "guanylyl" cyclase possesses much broader substrate specificity than previously assumed...
  58. pmc SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1
    Michelle Pacholec
    Department of Cardiovascular, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    J Biol Chem 285:8340-51. 2010
    ..Taken together, we conclude that SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1...
  59. ncbi Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha
    D R Alessi
    Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee, DD1 4HN, Scotland
    Curr Biol 7:261-9. 1997
    ..The phosphorylation of both residues is required for maximal activation of PKB. The kinases that phosphorylate PKB are, however, unknown...
  60. pmc The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases
    P Mohaghegh
    Imperial Cancer Research Fund Laboratories, University of Oxford, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK
    Nucleic Acids Res 29:2843-9. 2001
    ..We interpret these data in the light of the genomic instability and hyper-recombination characteristics of cells from individuals with Bloom's or Werner's syndrome...
  61. ncbi A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB
    J A DiDonato
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
    Nature 388:548-54. 1997
    ..A component of IKK was molecularly cloned and identified as a serine kinase. IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-kappaB activation...
  62. pmc Structural basis of RNA recognition and activation by innate immune receptor RIG-I
    Fuguo Jiang
    Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, 679 Hoes Lane West, Piscataway, New Jersey 08854, USA
    Nature 479:423-7. 2011
    ..The structure yields unprecedented insight into innate immunity and has a broader impact on other areas of biology, including RNA interference and DNA repair, which utilize homologous helicase domains within DICER and FANCM...
  63. pmc Oxidoreductive cellulose depolymerization by the enzymes cellobiose dehydrogenase and glycoside hydrolase 61
    James A Langston
    Novozymes, Inc, 1445 Drew Avenue, Davis, California 95618, USA
    Appl Environ Microbiol 77:7007-15. 2011
    ..The action of GH61 and CDH on cellulose may constitute an important, but overlooked, biological oxidoreductive system that functions in microbial lignocellulose degradation and has applications in industrial biomass utilization...
  64. pmc Comprehensive identification of protein substrates of the Dot/Icm type IV transporter of Legionella pneumophila
    Wenhan Zhu
    Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America
    PLoS ONE 6:e17638. 2011
    ..Thus, our efforts have identified a large number of novel substrates of the Dot/Icm system and have revealed the diverse features recognizable by this protein transporter...
  65. ncbi Diversity in the serine recombinases
    Margaret C M Smith
    Institute of Genetics, Queens Medical Centre, University of Nottingham, NG7 2UH, UK
    Mol Microbiol 44:299-307. 2002
    ..These observations indicate that the serine recombinases are modular and that fusion of the catalytic domain to unrelated sequences has generated structural and functional diversity...
  66. ncbi Small ubiquitin-related modifier (SUMO)-specific proteases: profiling the specificities and activities of human SENPs
    Jowita Mikolajczyk
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 282:26217-24. 2007
    ..Using these synthetic substrates we reveal that the SUMO domain enhances catalysis of SENP1, -2, -5, -6, and -7, demonstrating substrate-induced activation of SENPs by SUMOs...
  67. ncbi MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine
    A van Helvoort
    Department of Cell Biology, Faculty of Medicine and Institute of Biomembranes, Universiteit Utrecht, The Netherlands
    Cell 87:507-17. 1996
    ..Since no vesicular secretion occurs at 15 degrees C, the short-chain lipids must have been translocated by the Pgps across the plasma membrane before extraction into the medium by the lipid-acceptor albumin...
  68. pmc Acetylation: a regulatory modification to rival phosphorylation?
    T Kouzarides
    Wellcome CRC Institute, Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QR, UK
    EMBO J 19:1176-9. 2000 acetylation a modification analogous to phosphorylation? This review sets out what we know about the broader substrate specificity and regulation of acetyl- ases and goes on to compare acetylation with the process of phosphorylation.
  69. pmc Executioner caspase-3 and caspase-7 are functionally distinct proteases
    John G Walsh
    Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland
    Proc Natl Acad Sci U S A 105:12815-9. 2008
    ..Our observations provide a molecular basis for the different phenotypes seen in mice lacking either caspase and indicate that these proteases occupy nonredundant roles within the cell death machinery...
  70. pmc Divergence and convergence in enzyme evolution: parallel evolution of paraoxonases from quorum-quenching lactonases
    Mikael Elias
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 287:11-20. 2012
  71. ncbi The MutT proteins or "Nudix" hydrolases, a family of versatile, widely distributed, "housecleaning" enzymes
    M J Bessman
    Department of Biology and The McCollum Pratt Institute, The Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Biol Chem 271:25059-62. 1996
  72. ncbi CDK activity antagonizes Whi5, an inhibitor of G1/S transcription in yeast
    Michael Costanzo
    Department of Medical Genetics and Microbiology, University of Toronto, 1 King s College Circle, Toronto, M5S 1A8, Canada
    Cell 117:899-913. 2004
    ..Elimination of CDK activity at the end of mitosis allows Whi5 to reenter the nucleus to again repress G1/S transcription. These findings harmonize G1/S control in eukaryotes...
  73. ncbi Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen
    Shawn E Lupold
    Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 2101, USA
    Cancer Res 62:4029-33. 2002
    ..These aptamers may be used clinically as NAALADase inhibitors or be modified to carry imaging agents and therapeutic agents directed to prostate cancer cells...
  74. ncbi Functions of site-specific histone acetylation and deacetylation
    Mona D Shahbazian
    Department of Biological Chemistry, Geffen School of Medicine and the Molecular Biology Institute, University of California, Los Angeles, California 90095, USA
    Annu Rev Biochem 76:75-100. 2007
    ..Determining how these enzymes create distinct acetylation patterns and regulate the functional outcome is an important challenge...
  75. doi What makes an enzyme promiscuous?
    Ann Babtie
    Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK
    Curr Opin Chem Biol 14:200-7. 2010
  76. ncbi Enzyme promiscuity: evolutionary and mechanistic aspects
    Olga Khersonsky
    Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel
    Curr Opin Chem Biol 10:498-508. 2006
  77. pmc A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA
    Paul C Blainey
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 103:5752-7. 2006
    ..5 kcal/mol (1 kcal = 4.2 kJ). This nearly barrierless Brownian sliding indicates that DNA glycosylases locate lesion bases by a massively redundant search in which the enzyme selectively binds 8-oxoguanine under kinetic control...
  78. ncbi A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes
    N A Thornberry
    Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065
    Nature 356:768-74. 1992
    ..Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1 beta, indicating that it is a potential therapeutic target...
  79. doi HtrA proteases have a conserved activation mechanism that can be triggered by distinct molecular cues
    Tobias Krojer
    Research Institute of Molecular Pathology, Vienna, Austria
    Nat Struct Mol Biol 17:844-52. 2010
    ..Implications for protein quality control and regulation of oligomeric enzymes are discussed...
  80. pmc Maintaining a sense of direction during long-range communication on DNA
    Mark D Szczelkun
    DNA Protein Interactions Unit, Department of Biochemistry, University of Bristol, Bristol BS8 1TD, UK
    Biochem Soc Trans 38:404-9. 2010
    ..The generality of this mechanism to other ATP-dependent communication processes such as mismatch repair is also discussed...
  81. ncbi Structural and sequence-based classification of glycoside hydrolases
    B Henrissat
    Centre de Recherches sur les Macromolecules Vegetales, CNRS, Joseph Fourier Université, Grenoble, France
    Curr Opin Struct Biol 7:637-44. 1997
    ..The recent analysis of these families, coupled with the burgeoning number of 3D structures, provides a detailed insight into the structure, function and catalytic mechanism of these enzymes...
  82. pmc Regulation of AKT phosphorylation at Ser473 and Thr308 by endoplasmic reticulum stress modulates substrate specificity in a severity dependent manner
    Hong Wa Yung
    Centre for Trophoblast Research, University of Cambridge, Cambridge, United Kingdom
    PLoS ONE 6:e17894. 2011
    ..Here, we demonstrate that ER stress modulates AKT substrate specificity in a severity-dependent manner, as shown by phospho-specific antibodies against known AKT targets...
  83. pmc Specificity prediction of adenylation domains in nonribosomal peptide synthetases (NRPS) using transductive support vector machines (TSVMs)
    Christian Rausch
    Center for Bioinformatics Tübingen ZBIT, University of Tubingen, Germany
    Nucleic Acids Res 33:5799-808. 2005
    We present a new support vector machine (SVM)-based approach to predict the substrate specificity of subtypes of a given protein sequence family...
  84. pmc Enzymatic and structural insights for substrate specificity of a family of jumonji histone lysine demethylases
    John R Horton
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA
    Nat Struct Mol Biol 17:38-43. 2010
    ..The difference in substrate specificity between the two is explained by PHF8 adopting a bent conformation, allowing each of its domains to engage ..
  85. ncbi Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition
    R Dajani
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom
    Cell 105:721-32. 2001
  86. ncbi DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected]
    C D Mol
    Skaggs Institute for Chemical Biology, and the Department of Molecular Biology, La Jolla, California 92037 1027, USA
    Nature 403:451-6. 2000
  87. ncbi Highly efficient endogenous human gene correction using designed zinc-finger nucleases
    Fyodor D Urnov
    Sangamo BioSciences, Inc, Pt Richmond Tech Center 501, Canal Blvd, Suite A100 Richmond, California 94804, USA
    Nature 435:646-51. 2005
    ..We observe comparably high frequencies in human T cells, raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease...
  88. ncbi The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases
    N R Brown
    Laboratory of Molecular Biophysics and Oxford Centre for Molecular Sciences, Department of Biochemistry, University of Oxford, Rex Richards Building, South Parks Road, Oxford OX1 3QU, UK
    Nat Cell Biol 1:438-43. 1999
    ..These residues include the RXL motif required to target p107 to cyclins. This structure explains the specificity of the RXL motif for cyclins...
  89. pmc NRPSpredictor2--a web server for predicting NRPS adenylation domain specificity
    Marc Röttig
    Applied Bioinformatics, Center for Bioinformatics, Department of Computer Science, University of Tubingen, Sand 14, 72076 Tubingen, Germany
    Nucleic Acids Res 39:W362-7. 2011
    ..The ability to predict substrate specificity of newly detected NRPS Adenylation (A-) domains by genome sequencing efforts is of great importance to ..
  90. pmc Mechanism of substrate selection by a highly specific CRISPR endoribonuclease
    Samuel H Sternberg
    Department of Chemistry, University of California, Berkeley, California 94720, USA
    RNA 18:661-72. 2012
    ..b>Substrate specificity is achieved by RNA major groove contacts that are highly sensitive to helical geometry, as well as a ..
  91. pmc Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing
    Gang Fang
    Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, USA
    Nat Biotechnol 30:1232-9. 2012
  92. pmc Creating highly specific nucleases by fusion of active restriction endonucleases and catalytically inactive homing endonucleases
    Ines Fonfara
    Institut fur Biochemie, Justus Liebig Universitat Giessen, Heinrich Buff Ring 58, D 35392, Giessen, Germany
    Nucleic Acids Res 40:847-60. 2012
  93. ncbi Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines
    M H Kuo
    Department of Biology, University of Rochester, New York 14627, USA
    Nature 383:269-72. 1996
  94. ncbi Determination of protease cleavage site motifs using mixture-based oriented peptide libraries
    B E Turk
    Department of Medicine, Beth Israel Deaconess Medical Center, Department of Cell Biology, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    Nat Biotechnol 19:661-7. 2001
    ..Our results indicate that a small set of libraries can be used to quickly profile an expanding protease family, providing information applicable to the design of inhibitors and to the identification of protein substrates...
  95. pmc Excision of misincorporated ribonucleotides in DNA by RNase H (type 2) and FEN-1 in cell-free extracts
    Bjorn Rydberg
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 99:16654-9. 2002
    ..Conversely, a highly purified archaeal RNase HII type 2 protein has a pronounced activity. To study substrate specificity, extracts were made from a yeast double mutant lacking the other main RNase H enzymes [RNase H1 and RNase ..
  96. pmc Design of protein-interaction specificity gives selective bZIP-binding peptides
    Gevorg Grigoryan
    MIT Department of Biology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nature 458:859-64. 2009
  97. pmc Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production
    Makiko Umezu-Goto
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    J Cell Biol 158:227-33. 2002
    ..It also provides potential novel targets for therapy of pathophysiological states including cancer...
  98. pmc Expanding or restricting the target site repertoire of zinc-finger nucleases: the inter-domain linker as a major determinant of target site selectivity
    Eva Maria Händel
    Charite Medical School, Institute of Virology CBF, Berlin, Germany
    Mol Ther 17:104-11. 2009
    ..In summary, both sequence and length of the inter-domain linker determine ZFN activity and target-site specificity, and are therefore important parameters to account for when designing ZFNs for genome editing...
  99. ncbi Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations
    R B Pearson
    Methods Enzymol 200:62-81. 1991
  100. ncbi Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast
    E Mossessova
    Biochemistry Department, Weill Medical College of Cornell University, New York, New York 10021, USA
    Mol Cell 5:865-76. 2000
    ..Genetic analysis guided by the structure further reveals a regulatory element N-terminal to the proteolytic domain that is required for cell growth in yeast...
  101. ncbi Pot1, the putative telomere end-binding protein in fission yeast and humans
    P Baumann
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA
    Science 292:1171-5. 2001
    ..It now appears that the protein that caps the ends of chromosomes is widely dispersed throughout the eukaryotic kingdom...

Research Grants68

    Buddy Ullman; Fiscal Year: 2003 mutant UPRT and AK proteins will also be carried out to assess the roles of key residues in substrate specificity and catalysis. Mutant enzymes will be purified from E...
  2. Role of SAMe on UBC9 and sumolyation in liver cancer and alcoholic liver injury
    Maria Lauda Tomasi; Fiscal Year: 2012
    ..the activated SUMO to the target protein and is believed to play an important role in regulating the substrate specificity and enhancing the efficiency of sumoylation in vivo...
  3. A novel peroxidase in vascular endothelium and the development of atherosclerosis
    Guangjie Cheng; Fiscal Year: 2012
    ..Aim #1 will purify VPO from mammalian cells stably overexpressing VPO and will characterize its basic substrate specificity and enzymatic properties...
  4. Microsomal Cytochromes P450 and their Interactions with their Redox Partners
    Lucy A Waskell; Fiscal Year: 2013
    ..P450, are to understand the biochemical basis of how the redox partners of cyt P450 regulate its activity, substrate specificity, and catalytic mechanism...
  5. The Effects of PP2A on TNF Signaling and Smoke-Induced Lung Injury
    Robert F Foronjy; Fiscal Year: 2013
    ..modifications of the C subunit and dynamic exchange of variable B subunits regulate PP2A substrate specificity, activity, and intracellular distribution...
    Shiou Chuan Tsai; Fiscal Year: 2010
    ..However, very little is known about the substrate specificity or biological functions of these pathogen ACCases...
  7. Structure and function of chloride channels and transporters
    Alessio Accardi; Fiscal Year: 2013
    ..Our second major aim is to identify the molecular basis of anionic selectivity in CLC proteins. Substrate specificity is of paramount importance to proper function of both channels and transporters...
  8. The Role of Cyp2b in Toxicant Metabolism and Sensitivity
    William S Baldwin; Fiscal Year: 2012
    ..Cyp2b is considered the forgotten CYP because not as much is known about its substrate specificity, it is expressed at lower levels in the liver than some other detoxification CYPs, and the FDA does not ..
  9. Organic Cation Transporter PMAT: Physiological Function and Role in Drug Disposit
    Joanne Wang; Fiscal Year: 2013
    ..PMAT is highly expressed in the brain and the gastrointestinal tract, and has overlapping substrate specificity with organic cation transporters 1- 3 (OCT1-3)...
  10. Functions of the Human OST-alpha and OST-beta Proteins
    Patricia M Hinkle; Fiscal Year: 2013
    ..Our studies to date of the transporter's substrate specificity, transport mechanism, tissue distribution, subcellular localization, transcriptional regulation, as well ..
  11. Enzymology of Post-translational Modifications
    Carol A Fierke; Fiscal Year: 2013
    ..Here, we propose to: (1) investigate determinants of prenyltransferase substrate specificity for mammalian and Candida albicans enzymes and analyze the effects of individual prenylation pathway ..
  12. Cleavage Products of Dietary Carotenoids: Occurrence &Nutritional Function
    EARL HOWARD HARRISON; Fiscal Year: 2013
    ..We will address these gaps in knowledge. (1) We determine the substrate specificity and characterize the products of the two known human carotenoid-metabolizing enzymes (BCO1 &BCO2)...
  13. Mechanisms of viral proteases in coronavirus replication and pathogenesis
    Andrew D Mesecar; Fiscal Year: 2013
    ..that distinct residues within the papain-like protease domain of coronaviruses are critical for mediating substrate specificity and interferon antagonism and that identification of these sites will provide novel targets for antiviral ..
  14. Kynurenic Acid Synthesis in Mouse Brain
    Jianyong Li; Fiscal Year: 2010
    ..The specific aims of this research proposal are: (1) to analyze the substrate specificity and catalytic efficiency of the currently identified KATs to kynurenine and other substrates through the ..
  15. Expression of clp genes in Streptococcus mutans
    Indranil Biswas; Fiscal Year: 2013
    ..While the ATPase component determines the substrate specificity, ClpP degrades the damaged protein. In most pathogens, ClpP plays a very important role in virulence...
  16. Cell wall synthesis enzymes and beta-lactam resistance in Enterococcus faecium
    Louis B Rice; Fiscal Year: 2013
    ..faecium autolysins 3) We will explore the molecular basis for the substrate specificity of Ldtfm to understand the surprising pattern of inhibition of the enzyme by ?-lactams 4) We will ..
  17. The Roles of Trm9 and tRNA Methylation in the DNA Damage Response
    Thomas J Begley; Fiscal Year: 2010
    ..Specifically, we will determine the damage-induced substrate specificity of S...
  18. BETR Therapy for Herpesvirus-Associated Tumors
    Martin G Pomper; Fiscal Year: 2013
    ..Because the substrate specificity for the viral TK is orthogonal to that of cellular TK, we can use a radiotherapeutic version of the virus-..
  19. Mammalian Mitochondrial One-Carbon Metabolism
    DEAN RAMSAY APPLING; Fiscal Year: 2010
    ..The MTHFD2L protein will be purified for analysis of its kinetics and substrate specificity. The expression profile of the gene in human and mouse tissues and mouse embryos will be examined...
  20. Fundamental mechanisms of protein kinase activation loop autophosphorlyation
    Vaughn Cleghon; Fiscal Year: 2013
    ..The intermediates differ in residue and substrate specificity, and sensitivity to small-molecule inhibitors, compared to their mature counterpart...
    ANTHONY PEGG; Fiscal Year: 2009
    ..There are four interrelated specific aims: (1) To understand the mechanism of action and substrate specificity of the aminopropyltransferase enzymes...
  22. Studies toward the development of monoamine oxidase B specific inhibitors
    ERIKA MARIE MILCZEK; Fiscal Year: 2010
    ..the structure/function relationships of MAO B by identifying amino acid residues responsible for its substrate specificity and designing specific inhibitors that target the enzyme as neuroprotecting agents...
  23. Reversible phosphorylation in Hedgehog signaling
    ALAN ZHU; Fiscal Year: 2013
    ..PP2A substrate specificity is conferred by its associated variable regulatory subunits...
  24. Reactivity epitopes of ribonuclease III substrates
    ALLEN WHITALL NICHOLSON; Fiscal Year: 2010
    ..Specific Aim 2 will characterize protein functional group contributions to substrate specificity and binding energy...
  25. Role of Ca2+/Calcineurin Signaling in S. cerevisiae
    Martha S Cyert; Fiscal Year: 2013
    ..These mutants will provide new tools for investigating CN function and substrate specificity in many organisms. 3) Identify the role of CN-interacting proteins in CN signaling pathways...
  26. Function of Laccases in Anopheles gambiae
    Michael R Kanost; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Project summary: Laccases are copper-containing oxidases with broad substrate specificity. They have been implicated in a variety of physiological processes in plants and fungi, including lignin ..
    Jeffrey D Esko; Fiscal Year: 2010
    ..extent on the composition and fine structure of the heparan sulfate chains, which in turn depend on the substrate specificity of the various biosynthetic enzymes and regulatory factors...
  28. Mycobacterium turberculosis metal transport P-type ATPases
    JOSE M ARGUELLO; Fiscal Year: 2010
    ..We hypothesize that the pathophysiological role of these transporters is primarily determined by their substrate specificity. Metal specificities of a subset of these P-type ATPases will be determined by expressing these in E...
  29. Engineering a packaging nanomotor for delivery of RNA and other molecules
    Venigalla B Rao; Fiscal Year: 2010 the high-throughput screen will be purified and analyzed for packaging ATPase, efficiency, and substrate specificity. Structural modeling of the mutant translocation grooves will be guided by the already determined crystal ..
  30. The regulation of ciliary motility by an axonemal PP2A phosphatase
    Candice Elam; Fiscal Year: 2011
    ..The B-subunit is responsible for providing the phosphatase with substrate specificity and sub-cellular localization...
  31. Structural and biochemical characterization of the OprD membrane protein family
    Bert van den Berg; Fiscal Year: 2011
    ..we will determine the X-ray crystal structures of a number of OprD-family channels and characterize their substrate specificity using a range of computational, biochemical and biophysical experiments...
  32. The Effect of Genetic Diversity on Mechanism-Based Inactivation of CYP2D6
    Laura L Furge; Fiscal Year: 2013
    ..One caveat of such broad substrate specificity among drug metabolizing CYPs is that the enzymes are susceptible to inhibition by products of their own ..
  33. In Vivo Regulation and Inhibition of Ribonucleotide Reductase
    Mingxia Huang; Fiscal Year: 2012
    ..R1 subunit binds the four NDP substrates as well as the allosteric effectors (NTPs and dATP) that govern substrate specificity and turnover rate, and the R2 subunit houses the essential tyrosyl radical required to initiate nucleotide ..
  34. Mitochondrial Fission in Huntington's Disease
    ELLA R BOSSY-WETZEL; Fiscal Year: 2013
    ..Persistent Cdk5 activation by p25 and aberrant Cdk5 subcellular localization and substrate specificity also contribute to neurodegeneration...
  35. Structural and Functional Studies of the Sac Family Phosphoinositide Phosphatases
    Yuxin Mao; Fiscal Year: 2013
    ..example, Sac domains in different proteins prefer a specific subgroup of PIs as substrates, but how the substrate specificity is determined by the otherwise homologous Sac domains is unresolved...
  36. mRNA Capping Enzymes
    STEWART H SHUMAN; Fiscal Year: 2013
    ..In this project, we propose to dissect genetically and biochemically the phosphoprotein substrate specificity of S. pombe Fcp1 and the requirements for Fcp1 function in vivo.
  37. Understanding aromatic hydrocarbon uptake as the first step in biodegradation
    Bert van den Berg; Fiscal Year: 2013
    ..2. To determine the structural basis for the substrate specificity of FadL channels. 3. To assess the importance of FadL channels for biodegradation. 4...
  38. Analysis of metallo-beta-lactamase sequence constraints at high resolution
    Timothy Palzkill; Fiscal Year: 2013
    ..e., residues that control substrate specificity. As these comparisons are made for each of the active site positions, a high resolution picture of the ..
  39. Structure and Function of HAD Phosphatase Partners Dullard and Lipin
    Debra Dunaway-Mariano; Fiscal Year: 2013
    ..of dullard-catalyzed dephosphorylation of phospholipin1 and lipin1-derived phosphopeptides will define substrate specificity. X-ray structure determination of dullard-substrate/transition state analog complexes will identify ..
  40. Mechanisms of Polycomb Silencing
    Yi Zhang; Fiscal Year: 2010
    ..Understand the PRC2 substrate specificity, processivity, and methyl-H3K27 inheritance...
  41. Understanding the roles of histone demethylation in germline maintenance
    SARA ELIZABETH BEESE-SIMS; Fiscal Year: 2013
    ..Specifically, we propose: 1) To biochemically and biologically determine the substrate specificity of the C...
  42. Mechanistic insights into cellular metal detoxification
    Jaekwon Lee; Fiscal Year: 2013 that this P-type ATPase is the first cadmium-specific efflux pump that is unique in structure, substrate specificity, and mode of regulation. This hypothesis will be tested using a multi-disciplinary approach...
  43. Structural insights into pandemic and emerging influenza viruses
    Ian A Wilson; Fiscal Year: 2013
    ..Using a novel strategy to investigate both HA and NA substrate specificity and activity using newly designed glycan microarrays, we will assess the functional relationships between ..
    Peter C Maloney; Fiscal Year: 2012 transporters during substrate binding and transport and (b) how such transporters establish their substrate specificity. Such information should make it easier to both diagnose disease and design interventions for treatment...
  45. Protein kinase C-delta actions in cardiomyocytes
    Susan F Steinberg; Fiscal Year: 2013 identify post-translational modifications that regulate PKC4 catalytic activity, and particularly its substrate specificity. Specific aim II will use RNAi silencing and adenoviral-mediated overexpression strategies to determine ..
  46. Structural basis of tetracycline resistance by efflux pump TetL
    DANENG WANG; Fiscal Year: 2013
    ..II). To understand the structural basis of TetL's substrate specificity, we will characterize key tetracycline-binding residues using a combination of structural, computational, ..
  47. Mechanisms linking the hemostatic protease thrombin to arthritic disease
    Matthew J Flick; Fiscal Year: 2013
    ..two mechanisms by which thrombin exacerbates inflammatory joint disease, and (3) "re-engineering" thrombin substrate specificity to promote anticoagulant/anti-inflammatory activity over procoagulant activity will convert the enzyme ..
  48. Metabolism of Short Chain Acyl-CoA and its Deficiency
    Gerard Vockley; Fiscal Year: 2013
    ..Specific aim 1b is to characterize the substrate specificity of the two primary products of ACD10 and 11...
  49. Molecular bssis of mef-mediated antibiotic resistance in Streptococcus pneumoniae
    David S Stephens; Fiscal Year: 2010
    ..In Specific Aim 1, the molecular basis, regulation and substrate specificity of the efflux pump will be determined and the pump's potential role as a virulence factor assessed...
  50. Mechanistic Studies of EGFR/ErbB Receptor Tyrosine Kinases
    Daniel J Leahy; Fiscal Year: 2013
    ..of activated EGFR, (iii) the influence of EGFR glycosylation and the EGFR C-tail on EGFR activity and substrate specificity, and (iv) the in vitro substrates of EGFR and mutant EGFRs using a 17,000 protein microarray...
  51. Targeting DXP Synthase in Non-mammalian Isoprenoid Biosynthesis
    FRANCINE M MORRIS; Fiscal Year: 2012
    ..This proposal discusses the results of initial substrate specificity studies which reveal a remarkable affinity of the enzyme for naphthol-based substrates...
    RONALD DREW ETHERIDGE; Fiscal Year: 2013
    ..insight into additional factors which may play a role in regulating kinase function or determining substrate specificity. In summary this project will integrate various phenotypic analyses, host cell transcriptional profiling, ..
  53. Understanding the impact of Antigen 85 complex substrate specificity on mycobacte
    DONALD RONNING; Fiscal Year: 2010
    ..antigen 85 enzymes and their substrates, identify components of each enzyme that lead to differences in substrate specificity, identify inhibitors of the catalytic activity, and combine these data to develop novel lead compounds for ..
  54. Aldo-keto reductase family 1 member B10 AKR1B10 in pancreatic carcinogenesis
    Guang Yu Yang; Fiscal Year: 2013
    ..AKR1B10 exhibits more restricted substrate specificity than that of most human AKR: only farnesal, geranylgeranial, retinal and carbonyls are its specific ..
  55. Mechanism and function of a conserved bacterial cyclic-di-GMP receptor system
    Richard B Cooley; Fiscal Year: 2013
    ..We will also develop an innovative assay to identify the substrate(s) and substrate specificity of LapG orthologs by introducing photo-crosslinking non-canonical amino acids (Specific Aim 2)...
  56. Purine Nucleoside/Nucleobase Transporters in Leishmania
    Scott Landfear; Fiscal Year: 2013
    ..1 that are non-functional in transport or have altered substrate specificity. These mutants will be examined for those that are non-functional because they fail to bind substrate and ..
  57. Regulation of IGF-1 by Human GRP94
    MICHAL TOMASZ MARZEC; Fiscal Year: 2013
    ..Ser/Thr phosphorylations) of GRP94 that occur in the lumen of ER and relate to its activity and substrate specificity (i.e. secretion of IGF-1). To date, the feasibility of each of these aims has been demonstrated...
    L David Sibley; Fiscal Year: 2013
    ..We will also employ biochemical assays and mass spectrometry to identify the substrate specificity of ROP kinases, there by providing specific substrates for development of inhibitor assays...
  59. DNA Methylation & Chromatin Modifications: Mechanisms & Applications in Cancer*
    Samson T Jacob; Fiscal Year: 2010
    ..Project 5 will focus on biochemical characterization of the activity and substrate specificity of the Brg1 and hBrm-associated PRMT5, identification of common target genes regulated by PRMTS-containing ..
  60. The Rosetta Enzyme ReDesign: Targeting PON1 as OP Scavenger
    Jennifer M Bui; Fiscal Year: 2012
    ..2) identifying conformational diversities of the enzyme, 3) exploring the effects of polymorphisms on substrate specificity and stability, and 4) integrating these enzymatic properties into the Rosetta Enzyme Design method [10, 11]..
  61. IgA Protease as Therapy to Reverse IgA Nephropathy
    Jiazhou Qiu; Fiscal Year: 2012
    ..Bacterial IgA proteases all have unique substrate specificity for human IgA1...
  62. Functional Characterization of an ER-Resident Ubiquitin Ligase in Yeast
    DAVID JAMES ADLE; Fiscal Year: 2011
    ..Doa10 shares similar morphology and substrate specificity with its human orthologue, TEB4/MARCH6, making its study highly relevant...
  63. Cellular Efflux and Metabolism of Protease Inhibitors
    Ashim Mitra; Fiscal Year: 2004
    ..capillary endothelial cells, P-gp and CYP3A4 in mature enterocytes and alveolar cells and their similar substrate specificity suggest that the function of these proteins may be complementary and may form a coordinated intestinal, ..
  64. Chemically Interrogating Clostridium difficile Glucosylating Toxin Activation
    Aimee Shen; Fiscal Year: 2010
    ..novel protease family and have begun developing these inhibitors into chemical probes to study protease substrate specificity and function...
    Rochelle Hanley; Fiscal Year: 1992
    Calcium-calmodulin dependent protein kinase II) (CaM-KII) is a widely distributed enzyme with a broad substrate specificity. Recent studies from our laboratory have demonstrated the presence of CaM-KII in cells of the rabbit renal ..
  66. Substrate Selection in Homologous Bacterial Transporters
    Manuel Varela; Fiscal Year: 2004
    ..Transporters have substrate specificity, which is poorly understood, thus hindering our understanding of transport...
  67. Transcriptional Regulation of Matrix Metalloproteinase-3 (MMP-3)
    RUTH BORGHAEI; Fiscal Year: 2007
    ..MMP-3 has broad substrate specificity and can activate other pro-MMP...
  68. Structure and Mechanism of Pathogen SET Domain HKMTs
    Ming Ming Zhou; Fiscal Year: 2009
    ..However, the catalytic mechanism and substrate specificity of these histone modifying enzymes are still not well understood...