substrate specificity

Summary

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. 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
  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. 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
  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 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
  8. ncbi 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
  9. 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
  10. 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

Detail Information

Publications339 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 (http://rebase.neb.com) and selected compilations can be downloaded by ftp (ftp.neb.com). Additionally, monthly updates can be requested via email...
  2. 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...
  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. 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
    ....
  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 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?..
  8. ncbi 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...
  9. 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...
  10. 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 ..
  11. 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...
  12. 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...
  13. 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...
  14. 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...
  15. ncbi 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...
  16. 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
    ....
  17. 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.
  18. 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...
  19. 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...
  20. 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...
  21. 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...
  22. 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...
  23. 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
    ....
  24. 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...
  25. 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...
  26. 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...
  27. pmc Protein kinase CK2: structure, regulation and role in cellular decisions of life and death
    David W Litchfield
    Department of Biochemistry, Siebens Drake Research Institute, University of Western Ontario, London, Ontario, Canada N6A 5C1
    Biochem J 369:1-15. 2003
    ..Furthermore, this anti-apoptotic function of CK2 may contribute to its ability to participate in transformation and tumorigenesis...
  28. 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...
  29. 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...
  30. 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...
  31. 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
    ....
  32. 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...
  33. 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
    ....
  34. ncbi 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
    ....
  35. 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...
  36. 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...
  37. 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...
  38. 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...
  39. 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
    ....
  40. 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...
  41. 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
    ....
  42. 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
    ..is 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.
  43. 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
    ....
  44. 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...
  45. 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 ..
  46. 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...
  47. 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
    ....
  48. 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
    ....
  49. doi An unbiased genome-wide analysis of zinc-finger nuclease specificity
    Richard Gabriel
    Department of Translational Oncology, National Center for Tumor Diseases NCT and German Cancer Research Center DKFZ, Heidelberg, Germany
    Nat Biotechnol 29:816-23. 2011
    ..Comprehensive mapping of ZFN activity in vivo will facilitate the broad application of these reagents in translational research...
  50. 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...
  51. 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...
  52. 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
    ....
  53. ncbi Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations
    R B Pearson
    Methods Enzymol 200:62-81. 1991
  54. pmc PMAP: databases for analyzing proteolytic events and pathways
    Yoshinobu Igarashi
    The Center on Proteolytic Pathways, The Cancer Research Center and The Inflammatory and Infectious Disease Center, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Nucleic Acids Res 37:D611-8. 2009
    ..Here, we describe how the databases of PMAP can be used to foster understanding of proteolytic pathways, and equally as significant, to reason about proteolysis...
  55. ncbi The yeast Pif1p helicase removes telomerase from telomeric DNA
    Jean Baptiste Boulé
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    Nature 438:57-61. 2005
    ..We propose that Pif1p helicase activity limits telomerase action both in vivo and in vitro by displacing active telomerase from DNA ends...
  56. 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...
  57. ncbi Design and evolution of new catalytic activity with an existing protein scaffold
    Hee Sung Park
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1, Kusung dong, Yusung Gu, Daejon 305 701, Korea
    Science 311:535-8. 2006
    ..8 x 10(2) (mole/liter)(-1) second(-1), thus increasing resistance to Escherichia coli growth on cefotaxime by a factor of about 100...
  58. ncbi Substrate specificity and gene expression of the amino-acid permeases in Saccharomyces cerevisiae
    B Regenberg
    Department of Yeast Genetics, Carlsberg Laboratory, Copenhagen Valby, Denmark
    Curr Genet 36:317-28. 1999
    ..one or more of the 20 common L-alpha-amino acids was studied in order to obtain a complete picture of the substrate specificity for these permeases...
  59. ncbi Identification of a gene coding for a deglycosylating enzyme in Hypocrea jecorina
    Ingeborg Stals
    Department of Biochemistry and Microbiology, Faculty of Applied Engineering Sciences, Ghent University, Ghent, Belgium
    FEMS Microbiol Lett 303:9-17. 2010
    ..This ENGase activity, not coregulated with cellulase production, could be responsible for the extensive N-deglycosylation observed for several T. reesei cellulases...
  60. pmc A unique family of Mrr-like modification-dependent restriction endonucleases
    Yu Zheng
    New England Biolabs, Inc, 240 County Road, Ipswich, MA, 01938, USA
    Nucleic Acids Res 38:5527-34. 2010
    ..The MspJI enzyme family, with their different recognition specificities and cleavage properties, provides a basis on which many future methods can build to decode the epigenomes of different organisms...
  61. pmc Unlocking the sugar "steric gate" of DNA polymerases
    Jessica A Brown
    Department of Biochemistry, Ohio State University, Columbus, Ohio 43210, United States
    Biochemistry 50:1135-42. 2011
    ..These important findings are summarized in this review...
  62. ncbi Selenocysteine lyase, a novel enzyme that specifically acts on selenocysteine. Mammalian distribution and purification and properties of pig liver enzyme
    N Esaki
    J Biol Chem 257:4386-91. 1982
    ..L-Cysteine (Ki, 1.0 mM) competes with L-selenocysteine (Km, 0.83 mM) to inhibit the enzyme reaction. The enzyme is the first proven enzyme that specifically acts on selenium compounds...
  63. pmc A robust and extracellular heme-containing peroxidase from Thermobifida fusca as prototype of a bacterial peroxidase superfamily
    Edwin van Bloois
    Laboratory of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747, AG, Groningen, The Netherlands
    Appl Microbiol Biotechnol 86:1419-30. 2010
    ..In conclusion, the detailed biochemical characterization reported here contributes significantly to our understanding of these enzymes and further emphasizes their biotechnological potential...
  64. pmc Ligand binding and substrate discrimination by UDP-galactopyranose mutase
    Todd D Gruber
    Department of Biochemistry, University of Wisconsin Madison, Madison, WI 53706 1544, USA
    J Mol Biol 391:327-40. 2009
    ..To understand the consequences of these differences, we derived a model for the productive UGM-substrate complex that highlights interactions that can contribute to catalysis and substrate discrimination...
  65. pmc Phylogenetic analyses suggest multiple changes of substrate specificity within the glycosyl hydrolase 20 family
    Jari Intra
    Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita di Milano, Via Celoria 26, 20133 Milano, Italy
    BMC Evol Biol 8:214. 2008
    ..Nevertheless, only limited analyses of phylogenetic relationships between GH20 genes have been performed until now...
  66. pmc Synthesis of novel lipids in Saccharomyces cerevisiae by heterologous expression of an unspecific bacterial acyltransferase
    Rainer Kalscheuer
    Institut fur Molekulare Mikrobiologie und Biotechnologie, Westfalische Wilhelms Universitat, Munster, Germany
    Appl Environ Microbiol 70:7119-25. 2004
    ..calcoaceticus ADP1, indicating the broad biocatalytic potential of this enzyme for biotechnological production of a large variety of lipids in vivo in prokaryotic as well as eukaryotic expression hosts...
  67. pmc A Legionella pneumophila-translocated substrate that is required for growth within macrophages and protection from host cell death
    Rita K Laguna
    Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA
    Proc Natl Acad Sci U S A 103:18745-50. 2006
    ..Defective intracellular growth of the sdhA(-) mutant could be partially suppressed by the action of caspase inhibitors, but caspase-independent cell death pathways eventually aborted replication of the mutant...
  68. pmc Mammalian wax biosynthesis. II. Expression cloning of wax synthase cDNAs encoding a member of the acyltransferase enzyme family
    Jeffrey B Cheng
    Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 279:37798-807. 2004
    ..The data suggest that wax monoester synthesis in mammals involves a two step biosynthetic pathway catalyzed by fatty acyl-CoA reductase and wax synthase enzymes...
  69. pmc Inhibition of host vacuolar H+-ATPase activity by a Legionella pneumophila effector
    Li Xu
    Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America
    PLoS Pathog 6:e1000822. 2010
    ..Our results indicate that direct targeting of v-ATPase by secreted proteins constitutes a virulence strategy for L. pneumophila, a vacuolar pathogen of macrophages and amoebae...
  70. ncbi Protease degradomics: mass spectrometry discovery of protease substrates and the CLIP-CHIP, a dedicated DNA microarray of all human proteases and inhibitors
    Christopher M Overall
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    Biol Chem 385:493-504. 2004
    ....
  71. doi Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases
    Pilar Redondo
    Macromolecular Crystallography Group, Spanish National Cancer Research Centre CNIO, c Melchor Fdez Almagro 3, 28029 Madrid, Spain
    Nature 456:107-11. 2008
    ....
  72. pmc Targeting individual subunits of the FokI restriction endonuclease to specific DNA strands
    Kelly L Sanders
    Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, UK
    Nucleic Acids Res 37:2105-15. 2009
    ..The latter extends the range of enzymes for nicking specified strands at specific sequences, and may facilitate further applications of FokI in gene targeting...
  73. ncbi Regulation of p53 activity through lysine methylation
    Sergei Chuikov
    Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Nature 432:353-60. 2004
    ..The crystal structure of a ternary complex of Set9 with a p53 peptide and the cofactor product S-adenosyl-l-homocysteine (AdoHcy) provides the molecular basis for recognition of p53 by this lysine methyltransferase...
  74. ncbi Enzymatic action of prostate-specific antigen (PSA or hK3): substrate specificity and regulation by Zn(2+), a tight-binding inhibitor
    J Malm
    Section for Clinical Chemistry, Department of Laboratory Medicine, Lund University, University Hospital Malmo, Malmo, Sweden
    Prostate 45:132-9. 2000
    ..We characterized the substrate specificity and zinc-mediated inhibition of PSA.
  75. ncbi Outlook for cellulase improvement: screening and selection strategies
    Y H Percival Zhang
    Biological Systems Engineering Department, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
    Biotechnol Adv 24:452-81. 2006
    ..Herein, we hypothesize that continuous culture using insoluble cellulosic substrates could be a powerful selection tool for enriching beneficial cellulase mutants from the large library displayed on the cell surface...
  76. pmc Metallo-beta-lactamase fold within nucleic acids processing enzymes: the beta-CASP family
    Isabelle Callebaut
    Systèmes moléculaires et Biologie structurale, LMCP, CNRS UMR 7590, Universités Paris 6 et Paris 7, case 115, 4 place Jussieu, F 75252 Paris Cedex 05, France
    Nucleic Acids Res 30:3592-601. 2002
    ..and genome data also allowed us to unravel particular sequence features which are likely to be involved in substrate specificity, as well as to describe new but as yet uncharacterised members which may play critical roles in DNA and ..
  77. ncbi Coding of odors by a receptor repertoire
    Elissa A Hallem
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Cell 125:143-60. 2006
    ..The space provides a basis for predicting behavioral responses to odors...
  78. doi Cracking the phosphatase code: docking interactions determine substrate specificity
    Jagoree Roy
    Department of Biology, Stanford University, 371 Serra Mall, Stanford, CA 94305 5020, USA
    Sci Signal 2:re9. 2009
    Phosphoserine- and phosphothreonine-directed phosphatases display remarkable substrate specificity, yet the sites that they dephosphorylate show little similarity in amino acid sequence...
  79. 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...
  80. pmc Structure of the predominant protein arginine methyltransferase PRMT1 and analysis of its binding to substrate peptides
    Xing Zhang
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Structure 11:509-20. 2003
    ..Three peptide binding channels are identified: two are between the two domains, and the third is on the surface perpendicular to the strands forming the beta barrel...
  81. ncbi Analysis of the DNA substrate specificity of the human BACH1 helicase associated with breast cancer
    Rigu Gupta
    Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Biol Chem 280:25450-60. 2005
    We have investigated the DNA substrate specificity of BACH1 (BRCA1-associated C-terminal helicase). The importance of various DNA structural elements for efficient unwinding by purified recombinant BACH1 helicase was examined...
  82. pmc Generation of a nicking enzyme that stimulates site-specific gene conversion from the I-AniI LAGLIDADG homing endonuclease
    Audrey McConnell Smith
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, North Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 106:5099-104. 2009
    ..The cleavage mechanism, DNA-binding affinity, and substrate specificity profile of the nickase are similar to the wild-type enzyme...
  83. pmc Exploitation of binding energy for catalysis and design
    Summer B Thyme
    Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
    Nature 461:1300-4. 2009
    ..Our results illustrate how classical enzymology and modern protein design can each inform the other...
  84. pmc Abundant ribonucleotide incorporation into DNA by yeast replicative polymerases
    Stephanie A Nick McElhinny
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Proc Natl Acad Sci U S A 107:4949-54. 2010
    ....
  85. 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...
  86. doi Human cyclic nucleotide phosphodiesterases possess a much broader substrate-specificity than previously appreciated
    Daniel Reinecke
    Institute of Pharmacology, Medical School of Hannover, Hannover, Germany
    FEBS Lett 585:3259-62. 2011
    ..Using an HPLC-MS based assay, here, we show that human PDEs belonging to various families hydrolyze not only cAMP and cGMP but also other cyclic nucleotides...
  87. pmc The versatile thymine DNA-glycosylase: a comparative characterization of the human, Drosophila and fission yeast orthologs
    Ulrike Hardeland
    Institute of Molecular Cancer Research, University of Zurich, August Forel Strasse 7, Ch 8008 Zurich, Switzerland
    Nucleic Acids Res 31:2261-71. 2003
    ....
  88. ncbi L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity
    M S Shearman
    Department of Molecular Biology, Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, England
    Biochemistry 39:8698-704. 2000
    ..Specific and potent inhibitors of A beta PP gamma-secretase activity such as L-685,458 will enable important advances toward the identification and elucidation of the mechanism of action of this enigmatic protease...
  89. doi Updated biological roles for matrix metalloproteinases and new "intracellular" substrates revealed by degradomics
    Georgina S Butler
    Centre for Blood Research, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, BC, Canada
    Biochemistry 48:10830-45. 2009
    ..Here we review progress made in the field of degradomics and present a current view of the MMP degradome...
  90. ncbi Structure and catalytic mechanism of the human histone methyltransferase SET7/9
    Bing Xiao
    Structural Biology Group, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Nature 421:652-6. 2003
    ....
  91. ncbi Proteomics discovery of metalloproteinase substrates in the cellular context by iTRAQ labeling reveals a diverse MMP-2 substrate degradome
    Richard A Dean
    Department of Oral Biological and Medical Sciences, 4 401 Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada
    Mol Cell Proteomics 6:611-23. 2007
    ..Hence this advance in degradomics cell-based screens for native protein substrates casts new light on the roles for proteases in cell function...
  92. pmc Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases
    Ankit Gupta
    Program in Gene Function and Expression, Department of Biochemistry and Molecular Pharmacology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Nucleic Acids Res 39:381-92. 2011
    ....
  93. ncbi Cuticular wax biosynthesis in petunia petals: cloning and characterization of an alcohol-acyltransferase that synthesizes wax-esters
    Andrew King
    Donald Danforth Plant Science Center, 975 N Warson Road, St Louis, MO 63132, USA
    Planta 226:381-94. 2007
    ..In fact, the activity would be sufficient to produce most of the low molecular wax-esters present in petals, with methyl-esters being the exception. This work is the first characterization of a eukaryotic protein from the WS/DGAT family...
  94. doi Evolution of quaternary structure in a homotetrameric enzyme
    Michael D W Griffin
    School of Biological Sciences, University of Canterbury, Christchurch 8140, New Zealand
    J Mol Biol 380:691-703. 2008
    ....
  95. ncbi Basic and applied features of multicopper oxidases, CueO, bilirubin oxidase, and laccase
    Takeshi Sakurai
    Division of Material Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa 920 1192, Japan
    Chem Rec 7:220-9. 2007
    ..The substrate specificity of MCO for organic substrates is produced by the integrated effects of the shape of the substrate-binding ..
  96. ncbi Identification of two novel human acyl-CoA wax alcohol acyltransferases: members of the diacylglycerol acyltransferase 2 (DGAT2) gene superfamily
    Aaron R Turkish
    Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA
    J Biol Chem 280:14755-64. 2005
    ..In situ hybridizations demonstrate a differentiation-specific expression pattern within the human sebaceous gland for the two AWAT genes, consistent with a significant role in the composition of sebum...
  97. doi Substrate specificity of family 5, 6, 7, 9, 12, and 45 endoglucanases
    E Vlasenko
    Novozymes Inc, Davis, CA 95618, USA
    Bioresour Technol 101:2405-11. 2010
    ....
  98. pmc The wax ester synthase/acyl coenzyme A:diacylglycerol acyltransferase from Acinetobacter sp. strain ADP1: characterization of a novel type of acyltransferase
    Tim Stöveken
    Institut fur Molekulare Mikrobiologie und Biotechnologie, Westfalische Wilhelms Universitat Munster, Corrensstr 3, D 48149 Munster, Germany
    J Bacteriol 187:1369-76. 2005
    ..Purified WS/DGAT revealed a remarkably low substrate specificity, accepting a broad range of various substances as alternative acceptor molecules...
  99. pmc Sequence-specific intramembrane proteolysis: identification of a recognition motif in rhomboid substrates
    Kvido Strisovsky
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Mol Cell 36:1048-59. 2009
    ..Our work demonstrates that intramembrane proteases can be sequence specific and that genome-wide substrate prediction based on their recognition motifs is feasible...
  100. pmc Mechanism of histone methylation catalyzed by protein lysine methyltransferase SET7/9 and origin of product specificity
    Hao Bo Guo
    Department of Biochemistry and Cellular and Molecular Biology, Center of Excellence in Structural Biology, University of Tennessee, Knoxville, TN 37996 0840, USA
    Proc Natl Acad Sci U S A 104:8797-802. 2007
    ..The results of the simulations provide important insights into the catalytic process and lead to a better understanding of experimental observations concerning the origin of product specificity for PKMTs...
  101. pmc A guanine nucleobase important for catalysis by the VS ribozyme
    Timothy J Wilson
    Cancer Research UK Nucleic Acid Structure Research Group, MSI WTB complex, The University of Dundee, Dundee, UK
    EMBO J 26:2489-500. 2007
    ..This is closely similar to the probable mechanism of the hairpin ribozyme, and the active site arrangements for the two ribozymes appear topologically equivalent. This has probably arisen by convergent evolution...

Research Grants85

  1. MECHANISM-BASED DRUG SELECTION AND DESIGN: NUCLEOTIDE SA
    Buddy Ullman; Fiscal Year: 2003
    ..site-directed 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. MECHANISM BASED DRUG SELECTION AND DESIGN--NUCLEOTIDE SA
    Buddy Ullman; Fiscal Year: 1999
    ..site-directed 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...
  3. MECHANISM-BASED DRUG SELECTION AND DESIGN: NUCLEOTIDE SA
    Buddy Ullman; Fiscal Year: 2000
    ..site-directed 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...
  4. MECHANISM-BASED DRUG SELECTION AND DESIGN: NUCLEOTIDE SA
    Buddy Ullman; Fiscal Year: 2001
    ..site-directed 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...
  5. MECHANISM-BASED DRUG SELECTION AND DESIGN: NUCLEOTIDE SA
    Buddy Ullman; Fiscal Year: 2002
    ..site-directed 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...
  6. Cellular Efflux and Metabolism of Protease Inhibitors
    Ashim Mitra; Fiscal Year: 2002
    ..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, ..
  7. Cellular Efflux and Metabolism of Protease Inhibitors
    Ashim Mitra; Fiscal Year: 2003
    ..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, ..
  8. 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, ..
  9. STRUCTURE-BASED TUBERCULOSIS DRUG DESIGN TARGETED AT ACYL-COA CARBOXYLASE
    Shiou Chuan Tsai; Fiscal Year: 2009
    ..However, very little is known about the substrate specificity or biological functions of these pathogen ACCases...
  10. STRUCTURE-BASED TUBERCULOSIS DRUG DESIGN TARGETED AT ACYL-COA CARBOXYLASE
    Shiou Chuan Tsai; Fiscal Year: 2010
    ..However, very little is known about the substrate specificity or biological functions of these pathogen ACCases...
  11. ROBBINS Glycosylation and Glycosidases-Cell and Molecular Biology
    Phillips W Robbins; Fiscal Year: 2010
    ..Third, truncated N-glycans of the protists affect the substrate specificity of the oligosaccharyltransferase (OST) that transfers N-glycans from the lipid precursor to the nascent ..
  12. ROBBINS Glycosylation and Glycosidases-Cell and Molecular Biology
    PHILLIPS ROBBINS; Fiscal Year: 2009
    ..Third, truncated N-glycans of the protists affect the substrate specificity of the oligosaccharyltransferase (OST) that transfers N-glycans from the lipid precursor to the nascent ..
  13. The Effects of PP2A on TNF Signaling and Smoke-Induced Lung Injury
    Robert F Foronjy; Fiscal Year: 2010
    ..modifications of the C subunit and dynamic exchange of variable B subunits regulate PP2A substrate specificity, activity, and intracellular distribution...
  14. Functions of the Human OST-alpha and OST-beta Proteins
    Nazzareno Ballatori; Fiscal Year: 2010
    ..Our studies to date of the transporter's substrate specificity, transport mechanism, tissue distribution, subcellular localization, transcriptional regulation, as well ..
  15. Molecular Mechanisms of Dietary Fat Digestion by Pancreatic Lipases
    Mark E Lowe; Fiscal Year: 2010
    ..In this application, we will focus on the steps in lipolysis that influence substrate specificity. Lipases differ from esterases that act on water soluble substrates in that lipases must absorb to the ..
  16. A novel peroxidase in vascular endothelium and the development of atherosclerosis
    Guangjie Cheng; Fiscal Year: 2009
    ..Aim #1 will purify VPO from mammalian cells stably overexpressing VPO and will characterize its basic substrate specificity and enzymatic properties...
  17. Molecular Mechanisms of Dietary Fat Digestion by Pancreatic Lipases
    Mark Lowe; Fiscal Year: 2009
    ..In this application, we will focus on the steps in lipolysis that influence substrate specificity. Lipases differ from esterases that act on water soluble substrates in that lipases must absorb to the ..
  18. A novel peroxidase in vascular endothelium and the development of atherosclerosis
    Guangjie Cheng; Fiscal Year: 2010
    ..Aim #1 will purify VPO from mammalian cells stably overexpressing VPO and will characterize its basic substrate specificity and enzymatic properties...
  19. PERMEABILITY OF THE EPIDEMIC TYPHUS RICKETTSIA
    Herbert Winkler; Fiscal Year: 1991
    ..The putative components of rickettsial penetration (entry and exit) will be investigated: a) The substrate specificity and enzyme source (rickettsial or host) of the phospholipase will be characterized using liposomes which ..
  20. PERMEABILITY OF THE EPIDEMIC TYPHUS RICKETTSIA
    Herbert Winkler; Fiscal Year: 1990
    ..The putative components of rickettsial penetration (entry and exit) will be investigated: a) The substrate specificity and enzyme source (rickettsial or host) of the phospholipase will be characterized using liposomes which ..
  21. PERMEABILITY OF THE EPIDEMIC TYPHUS RICKETTSIA
    Herbert Winkler; Fiscal Year: 1993
    ..The putative components of rickettsial penetration (entry and exit) will be investigated: a) The substrate specificity and enzyme source (rickettsial or host) of the phospholipase will be characterized using liposomes which ..
  22. PERMEABILITY OF THE EPIDEMIC TYPHUS RICKETTSIA
    Herbert Winkler; Fiscal Year: 1992
    ..The putative components of rickettsial penetration (entry and exit) will be investigated: a) The substrate specificity and enzyme source (rickettsial or host) of the phospholipase will be characterized using liposomes which ..
  23. Structure and function of chloride channels and transporters
    Alessio Accardi; Fiscal Year: 2009
    ..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...
  24. Structure and function of chloride channels and transporters
    Alessio Accardi; Fiscal Year: 2010
    ..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...
  25. Structure and function of chloride channels and transporters
    Alessio Accardi; Fiscal Year: 2009
    ..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...
  26. ROLE OF S-ADENOSYLMETHIONINE ON UBC9 AND SUMOYLATION IN LIVER CANCER AND ALCOHOLI
    Maria Lauda Tomasi; Fiscal Year: 2010
    ..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...
  27. ISOMERASE, HYDROLASE AND REDUCTASE ENZYMES IN THE EYE
    Nicholas Bodor; Fiscal Year: 1992
    ..The oxime hydrolase activity and substrate specificity will be estimated in vitro and in vivo, using various oximes related to beta-adrenergic antagonists some ..
  28. GLUCOSE TRANSPORTER STRUCTURE AND FUNCTION
    Anthony Carruthers; Fiscal Year: 2010
    ..To do this, we must resolve: 1) Determinants of substrate specificity and their locations within GLUT architecture;2) How some transporters catalyze uniport while others ..
  29. GLUCOSE TRANSPORTER STRUCTURE AND FUNCTION
    Anthony Carruthers; Fiscal Year: 2009
    ..To do this, we must resolve: 1) Determinants of substrate specificity and their locations within GLUT architecture;2) How some transporters catalyze uniport while others ..
  30. 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...
  31. CHEMISTRY AND BIOLOGY OF GUT SOMATOSTATIN
    Tadataka Yamada; Fiscal Year: 1992
    ..The substrate specificity of the processing enzymes will be studies by mutating the key processing sites and examining the ..
  32. Biosynthesis of Microbial Polyketides
    David E Cane; Fiscal Year: 2010
    ..Special emphasis will be placed on 1) understanding the mechanism, substrate specificity, and stereochemistry of the reduction reactions catalyzed by ketoreductase (KR) domains;2) confirming the ..
  33. CALMODULIN KINASE II AND ION TRANSPORT IN THE KIDNEY
    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 ..
  34. 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...
  35. CYTOCHROME P-450 POLYMORPHISM
    Eric Johnson; Fiscal Year: 1993
    A major aim of the present application is to understand how the multi-substrate specificity of Class IIC cytochrome P450 enzymes is encoded in their primary and tertiary structures...
  36. CYTOCHROME P-450 POLYMORPHISM
    Eric Johnson; Fiscal Year: 1990
    A major aim of the present application is to understand how the multi-substrate specificity of Class IIC cytochrome P450 enzymes is encoded in their primary and tertiary structures...
  37. CYTOCHROME P-450 POLYMORPHISM
    Eric Johnson; Fiscal Year: 1991
    A major aim of the present application is to understand how the multi-substrate specificity of Class IIC cytochrome P450 enzymes is encoded in their primary and tertiary structures...
  38. Functional and structural characterization of spliceosomal cyclophilins
    Tara L Davis; Fiscal Year: 2010
    ..characterized these proteins in terms of their catalytic activities in solution and hypothesized potential substrate specificity based on in silico modeling...
  39. CYTOCHROME P-450 POLYMORPHISM
    Eric Johnson; Fiscal Year: 1992
    A major aim of the present application is to understand how the multi-substrate specificity of Class IIC cytochrome P450 enzymes is encoded in their primary and tertiary structures...
  40. GENETIC CONTROL OF PROTEOGLYCAN METABOLISM
    Jeffrey Esko; Fiscal Year: 2006
    ..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...
  41. GENETIC CONTROL OF PROTEOGLYCAN METABOLISM
    Jeffrey Esko; Fiscal Year: 2003
    ..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...
  42. GENETIC CONTROL OF PROTEOGLYCAN METABOLISM
    Jeffrey Esko; Fiscal Year: 2002
    ..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...
  43. GENETIC CONTROL OF PROTEOGLYCAN METABOLISM
    Jeffrey Esko; Fiscal Year: 2003
    ..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...
  44. GENETIC CONTROL OF PROTEOGLYCAN METABOLISM
    Jeffrey Esko; Fiscal Year: 2000
    ..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...
  45. GENETIC CONTROL OF PROTEOGLYCAN METABOLISM
    Jeffrey Esko; Fiscal Year: 2004
    ..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...
  46. GENETIC CONTROL OF PROTEOGLYCAN METABOLISM
    Jeffrey Esko; Fiscal Year: 2001
    ..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...
  47. GENETIC CONTROL OF PROTEOGLYCAN METABOLISM
    Jeffrey Esko; Fiscal Year: 2000
    ..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...
  48. Mechanisms linking the hemostatic protease thrombin to arthritic disease
    Matthew J Flick; Fiscal Year: 2010
    ..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 ..
  49. Mechanisms linking the hemostatic protease thrombin to arthritic disease
    Matthew Flick; Fiscal Year: 2009
    ..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 ..
  50. 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...
  51. GENETIC CONTROL OF PROTEOGLYCAN METABOLISM
    Jeffrey Esko; Fiscal Year: 2007
    ..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...
  52. PROSTAGLANDIN 19- & 20-HYDROXYLATION BY CYTOCHROME P-450
    Bettie Sue Masters; Fiscal Year: 1991
    ..This unique heme protein exhibits a substrate specificity toward eicosanoids with oxygen-containing functional groups at the omega-6 position and regioselectively ..
  53. PROSTAGLANDIN 19- & 20-HYDROXYLATION BY CYTOCHROME P-450
    Bettie Sue Masters; Fiscal Year: 1992
    ..This unique heme protein exhibits a substrate specificity toward eicosanoids with oxygen-containing functional groups at the omega-6 position and regioselectively ..
  54. PROSTAGLANDIN 19- & 20-HYDROXYLATION BY CYTOCHROME P-450
    Bettie Sue Masters; Fiscal Year: 1993
    ..This unique heme protein exhibits a substrate specificity toward eicosanoids with oxygen-containing functional groups at the omega-6 position and regioselectively ..
  55. PROSTAGLANDIN 19- & 20-HYDROXYLATION BY CYTOCHROME P-450
    Bettie Sue Masters; Fiscal Year: 1990
    ..This unique heme protein exhibits a substrate specificity toward eicosanoids with oxygen-containing functional groups at the omega-6 position and regioselectively ..
  56. Enzymology of Post-translational Modifications
    Carol A Fierke; Fiscal Year: 2010
    ..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 ..
  57. Dissecting the substrate specificity of acyl-CoA carboxylase
    Shiou Chuan Tsai; Fiscal Year: 2010
    ..application, which is the next step toward our long-term goal, is to determine the molecular basis of substrate specificity of ACC and PCC from Streptomyces coelicolor. The S...
  58. HUMAN SERUM PARAOXONASE: ROLE IN PESTICIDE METABOLISM
    Clement Furlong; Fiscal Year: 1990
    ..and further characterization of human and rabbit serum paraoxonase/arylesterase; 2) further studies on the substrate specificity of the enzyme with particular emphasis on organophosphate pesticide substrates and possible physiological ..
  59. Structure and Mechanism of Pathogen SET Domain HKMTs
    Ming Ming Zhou; Fiscal Year: 2006
    ..However, the catalytic mechanism and substrate specificity of these histone modifying enzymes are still not well understood...
  60. Structure and Mechanism of Pathogen SET Domain HKMTs
    Ming Ming Zhou; Fiscal Year: 2007
    ..However, the catalytic mechanism and substrate specificity of these histone modifying enzymes are still not well understood...
  61. 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...
  62. SUBSTRATE SPECIFICITY AND REGULATION OF THROMBIN
    John Sheehan; Fiscal Year: 1993
    ..The effects of specific mutations on thrombin substrate specificity and the rate of thrombin inhibition by serpins will be determined by kinetic methods...
  63. DIETARY PUFA EFFECTS ON LCAT REACTIVITY
    John Parks; Fiscal Year: 1999
    ..aim, we will determine the regions of the LCAT protein that are important in determining the fatty acyl substrate specificity of LCAT. We will take advantage of the difference in substrate specificity between rodent and primate LCAT...
  64. MEMBRANE-BOUND DETOXICATION ENZYMES
    Richard Armstrong; Fiscal Year: 1993
    ..and detoxication of xenobiotics it is necessary to have a basic understanding of the mechanism of action, substrate specificity and structure of each enzyme that participates or could participate in metabolism...
  65. BETA LACTAMASE MUTATIONS IN ANTIBIOTIC RESISTANCE
    Timothy Palzkill; Fiscal Year: 2004
    ..It will be necessary to understand the catalytic mechanism and basis for substrate specificity of each class of B-lactamase...
  66. BETA LACTAMASE MUTATIONS IN ANTIBIOTIC RESISTANCE
    Timothy Palzkill; Fiscal Year: 2002
    ..It will be necessary to understand the catalytic mechanism and basis for substrate specificity of each class of B-lactamase...
  67. BETA LACTAMASE MUTATIONS IN ANTIBIOTIC RESISTANCE
    Timothy Palzkill; Fiscal Year: 2001
    ..It will be necessary to understand the catalytic mechanism and basis for substrate specificity of each class of B-lactamase...
  68. BETA LACTAMASE MUTATIONS IN ANTIBIOTIC RESISTANCE
    Timothy Palzkill; Fiscal Year: 2003
    ..It will be necessary to understand the catalytic mechanism and basis for substrate specificity of each class of B-lactamase...
  69. BETA LACTAMASE MUTATIONS IN ANTIBIOTIC RESISTANCE
    Timothy Palzkill; Fiscal Year: 2005
    ..It will be necessary to understand the catalytic mechanism and basis for substrate specificity of each class of B-lactamase...
  70. MOLECULAR CHARACTERIZATION OF ACYL-COA DEHYDROGENASES
    Gerard Vockley; Fiscal Year: 1993
    ..of structure/function relationships important in tetramerization of IVD and determination of substrate specificity of other ACD family members...
  71. Structural and biochemical characterization of the OprD membrane protein family
    Bert van den Berg; Fiscal Year: 2010
    ..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...
  72. Mechanism-based Inhibition of P450 2D6 by a Piperazine-containing Compound
    LAURA FURGE; Fiscal Year: 2009
    ..One caveat of such broad substrate specificity among drug metabolizing P450 enzymes is that the enzymes are also susceptible to inhibition by products of ..
  73. Structural and biochemical characterization of the OprD membrane protein family
    Bert van den Berg; Fiscal Year: 2009
    ..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...
  74. IgA Protease as Therapy to Reverse IgA Nephropathy
    Jiazhou Qiu; Fiscal Year: 2010
    ..Bacterial IgA proteases all have unique substrate specificity for human IgA1...
  75. Mechanism-based Inhibition of P450 2D6 by a Piperazine-containing Compound
    LAURA FURGE; Fiscal Year: 2009
    ..One caveat of such broad substrate specificity among drug metabolizing P450 enzymes is that the enzymes are also susceptible to inhibition by products of ..
  76. RAPAMYCIN BLOCKADE OF PROTEIN PHOSPHATASE SIGNALING
    DAVID BRAUTIGAN; Fiscal Year: 2001
    ..show that murine alpha-4 binds purified human PP2A, displaces the other regulatory subunits, and changes substrate specificity. Epitope tagged alpha-4 expressed in COS cells co-immunoprecipitated with PP2A and caused ..
  77. RAPAMYCIN BLOCKADE OF PROTEIN PHOSPHATASE SIGNALING
    DAVID BRAUTIGAN; Fiscal Year: 2000
    ..show that murine alpha-4 binds purified human PP2A, displaces the other regulatory subunits, and changes substrate specificity. Epitope tagged alpha-4 expressed in COS cells co-immunoprecipitated with PP2A and caused ..
  78. RAPAMYCIN BLOCKADE OF PROTEIN PHOSPHATASE SIGNALING
    DAVID BRAUTIGAN; Fiscal Year: 2002
    ..show that murine alpha-4 binds purified human PP2A, displaces the other regulatory subunits, and changes substrate specificity. Epitope tagged alpha-4 expressed in COS cells co-immunoprecipitated with PP2A and caused ..
  79. GLYCOGEN METABOLISM AND SIGNAL TRANSDUCTION IN YEAST
    Peter Roach; Fiscal Year: 2001
    ..ii) Substrate specificity of Pho85p cyclin dependent protein kinases...
  80. Structural basis of specificity in affinity-labeled polyketide synthase didomains
    Janet Smith; Fiscal Year: 2009
    ..of PKS domains to build synthetic pathways for novel compounds requires an understanding of the basis for substrate specificity and stereochemical outcome for each catalytic domain, which at present is lacking...
  81. Structural basis of specificity in affinity-labeled polyketide synthase didomains
    Janet L Smith; Fiscal Year: 2011
    ..of PKS domains to build synthetic pathways for novel compounds requires an understanding of the basis for substrate specificity and stereochemical outcome for each catalytic domain, which at present is lacking...