amino acid isomerases

Summary

Summary: Enzymes that catalyze either the racemization or epimerization of chiral centers within amino acids or derivatives. EC 5.1.1.

Top Publications

  1. ncbi Isolation of Bacillus subtilis (chungkookjang), a poly-gamma-glutamate producer with high genetic competence
    M Ashiuchi
    Department of Bioresources Science, Kochi University, Nankoku, Japan
    Appl Microbiol Biotechnol 57:764-9. 2001
  2. pmc Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis
    Paul M Kim
    The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 107:3175-9. 2010
  3. pmc Functional comparison of the two Bacillus anthracis glutamate racemases
    Dylan Dodd
    Department of Microbiology, Institute for Genomic Biology, University of Illinois, Urbana, IL 61801, USA
    J Bacteriol 189:5265-75. 2007
  4. ncbi Inhibition of Trypanosoma cruzi proline racemase affects host-parasite interactions and the outcome of in vitro infection
    Leticia Coutinho
    Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz FIOCRUZ, Av Brasil 4365, 21045 900 Rio de Janeiro, RJ, Brasil
    Mem Inst Oswaldo Cruz 104:1055-62. 2009
  5. ncbi Biochemical characterization of proline racemases from the human protozoan parasite Trypanosoma cruzi and definition of putative protein signatures
    Natalie Chamond
    Department of Immunology, Institut Pasteur, Paris 75724, France
    J Biol Chem 278:15484-94. 2003
  6. ncbi A poly-gamma-glutamate synthetic system of Bacillus subtilis IFO 3336: gene cloning and biochemical analysis of poly-gamma-glutamate produced by Escherichia coli clone cells
    M Ashiuchi
    Research Institute of Molecular Genetics, Kochi University, Nankoku, Kochi, 783 8502, Japan
    Biochem Biophys Res Commun 263:6-12. 1999
  7. pmc Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complexes
    D A Peattie
    Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139 4211
    Proc Natl Acad Sci U S A 89:10974-8. 1992
  8. ncbi Proline racemases are conserved mitogens: characterization of a Trypanosoma vivax proline racemase
    Nathalie Chamond
    Institut Pasteur, Laboratoire d Immunobiologie des Infections à Trypanosoma, Departement d Immunologie, Paris, France
    Mol Biochem Parasitol 165:170-9. 2009
  9. ncbi A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase
    M W Harding
    Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510
    Nature 341:758-60. 1989
  10. ncbi Regulation of peptide antibiotic production in Bacillus
    M A Marahiel
    Biochemie FB Chemie, Philipps Universitat Marburg, Germany
    Mol Microbiol 7:631-6. 1993

Research Grants

Scientific Experts

Detail Information

Publications163 found, 100 shown here

  1. ncbi Isolation of Bacillus subtilis (chungkookjang), a poly-gamma-glutamate producer with high genetic competence
    M Ashiuchi
    Department of Bioresources Science, Kochi University, Nankoku, Japan
    Appl Microbiol Biotechnol 57:764-9. 2001
    ..B. subtilis (chungkookjang) harbors no plasmid and is the first B. subtilis strain reported with both naturally high PGA productivity and high genetic competence...
  2. pmc Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis
    Paul M Kim
    The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 107:3175-9. 2010
    ..Because D-aspartate is a potential endogenous ligand for NMDA receptors, the loss of which elicits a phenotype resembling DR depletion, D-aspartate may function as a modulator of adult neurogenesis...
  3. pmc Functional comparison of the two Bacillus anthracis glutamate racemases
    Dylan Dodd
    Department of Microbiology, Institute for Genomic Biology, University of Illinois, Urbana, IL 61801, USA
    J Bacteriol 189:5265-75. 2007
    ..These results suggest that racE1 and racE2 encode functional glutamate racemases with similar, but not identical, active site features...
  4. ncbi Inhibition of Trypanosoma cruzi proline racemase affects host-parasite interactions and the outcome of in vitro infection
    Leticia Coutinho
    Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz FIOCRUZ, Av Brasil 4365, 21045 900 Rio de Janeiro, RJ, Brasil
    Mem Inst Oswaldo Cruz 104:1055-62. 2009
    ..cruzi proline racemase antibodies and the specific proline racemase inhibitor pyrrole-2-carboxylic acid significantly affect parasite infection of Vero cells in vitro. This inhibitor also hampers T. cruzi intracellular differentiation...
  5. ncbi Biochemical characterization of proline racemases from the human protozoan parasite Trypanosoma cruzi and definition of putative protein signatures
    Natalie Chamond
    Department of Immunology, Institut Pasteur, Paris 75724, France
    J Biol Chem 278:15484-94. 2003
    ....
  6. ncbi A poly-gamma-glutamate synthetic system of Bacillus subtilis IFO 3336: gene cloning and biochemical analysis of poly-gamma-glutamate produced by Escherichia coli clone cells
    M Ashiuchi
    Research Institute of Molecular Genetics, Kochi University, Nankoku, Kochi, 783 8502, Japan
    Biochem Biophys Res Commun 263:6-12. 1999
    ..coli cells harboring pgsBCA genes increased both the polymer production and D-glutamate content in the polymer. The polymer produced by the E. coli clone was higher in average molecular size than that produced by B. subtilis IFO 3336...
  7. pmc Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complexes
    D A Peattie
    Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139 4211
    Proc Natl Acad Sci U S A 89:10974-8. 1992
    ..FKBP52 transcripts are present in a variety of human tissues and could vary in abundance and/or stability...
  8. ncbi Proline racemases are conserved mitogens: characterization of a Trypanosoma vivax proline racemase
    Nathalie Chamond
    Institut Pasteur, Laboratoire d Immunobiologie des Infections à Trypanosoma, Departement d Immunologie, Paris, France
    Mol Biochem Parasitol 165:170-9. 2009
    ..Therefore the product of the novel TvPRAC gene identified in T. vivax and reported herein has the potential to be used as a drug target for this parasite-based trypanosomiasis...
  9. ncbi A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase
    M W Harding
    Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510
    Nature 341:758-60. 1989
    ....
  10. ncbi Regulation of peptide antibiotic production in Bacillus
    M A Marahiel
    Biochemie FB Chemie, Philipps Universitat Marburg, Germany
    Mol Microbiol 7:631-6. 1993
    ....
  11. ncbi Efficient gene inactivation in Bacillus anthracis
    Konstantin Y Shatalin
    Center for Pharmaceutical Biotechnology, University of Illinois, M C 870, 900 S Ashland Ave, Chicago, IL 60607, USA
    FEMS Microbiol Lett 245:315-9. 2005
    ..anthracis strain DeltaANR. Allelic replacements were observed at high frequencies, ranging from approximately 0.5% for racE2 up to 50% for racE1 and comEC. The system can be used for genetic validation of potential drug targets...
  12. ncbi Structural basis for glutamate racemase inhibition
    Kook Han Kim
    Life Sciences Division, Korea Institute of Science and Technology, 39 1 Hawolkok dong, Sungbuk Gu, Seoul, Korea
    J Mol Biol 372:434-43. 2007
    ..In both crystal forms, GluR exists as a dimer and the interactions seen at the dimer interface are almost identical. This agrees well with the results from gel filtration and dynamic light-scattering studies...
  13. pmc Staphylococcus haemolyticus contains two D-glutamic acid biosynthetic activities, a glutamate racemase and a D-amino acid transaminase
    M J Pucci
    Department of Microbiology, Bristol Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492 7660
    J Bacteriol 177:336-42. 1995
    ..These data suggest that S. haemolyticus, and probably S. aureus, contains genes for two D-glutamic acid biosynthetic activities, a glutamate racemase (dga gene) and a D-amino acid transaminase (dat gene)...
  14. ncbi Active site residues of glutamate racemase
    S Glavas
    Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada
    Biochemistry 40:6199-204. 2001
    ..An alternate possibility is that the residues may serve to stabilize the carbanionic intermediate in the racemization reaction...
  15. pmc Determinants of catalytic power and ligand binding in glutamate racemase
    M Ashley Spies
    Department of Biochemistry, Institute for Genomic Biology, University of Illinois, Urbana, Illinois 61801, USA
    J Am Chem Soc 131:5274-84. 2009
    ..Results from this study are important for laying the groundwork for discovery and design of high-affinity ligands to this class of cofactor-independent racemases...
  16. ncbi Regulation of the glutamate racemase of Escherichia coli investigated by site-directed mutagenesis
    P Doublet
    Laboratoire des Enveloppes Bactériennes et Peptides, URA 1131 CNRS, Universite Paris Sud, Orsay, France
    Microb Drug Resist 2:43-9. 1996
    ..The attractive hypothesis that the characteristic N-terminal amino acid extension (20 residues) of the E. coli enzyme could be involved in its activation by the nucleotide precursor is disproved by these experiments...
  17. pmc Nature of allosteric inhibition in glutamate racemase: discovery and characterization of a cryptic inhibitory pocket using atomistic MD simulations and pKa calculations
    Katie L Whalen
    Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
    J Phys Chem B 115:3416-24. 2011
    ..The potential for future drug development is discussed...
  18. ncbi New insights into the reaction mechanism catalyzed by the glutamate racemase enzyme: pH titration curves and classical molecular dynamics simulations
    Eduard Puig
    Departament de Química and Institut de Biotecnologia i de Biomedicina, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain
    J Phys Chem B 111:2385-97. 2007
    ..To study the consistency of this mechanism classical molecular dynamics (MD) simulations have been carried out along with pK1/2 calculations on the MD-generated structures...
  19. ncbi Design of Helicobacter pylori glutamate racemase inhibitors as selective antibacterial agents: a novel pro-drug approach to increase exposure
    Gregory S Basarab
    Cancer and Infection Research Area, AstraZeneca R and D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA
    Bioorg Med Chem Lett 18:4716-22. 2008
    ..In order to achieve high bioavailability, a novel pro-drug approach was implemented wherein a solubilizing sulfoxide moiety is oxidized in vivo to a sulfone...
  20. ncbi Substrate-induced conformational changes in Bacillus subtilis glutamate racemase and their implications for drug discovery
    Sergey N Ruzheinikov
    Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, United Kingdom
    Structure 13:1707-13. 2005
    ....
  21. ncbi Expression of glr gene encoding glutamate racemase in Bacillus licheniformis WX-02 and its regulatory effects on synthesis of poly-γ-glutamic acid
    Feng Jiang
    State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, People s Republic of China
    Biotechnol Lett 33:1837-40. 2011
    ..This is the first report that overexpression of the glr gene could enhance the L- and D-glutamate conversion in B. licheniformis WX-02 and increase the proportion of D-glutamate in γ-PGA and the yield of γ-PGA...
  22. ncbi Biochemistry and molecular genetics of poly-gamma-glutamate synthesis
    M Ashiuchi
    Department of Bioresources Science, Kochi University, Nankoku, Kochi, 783 8502, Japan
    Appl Microbiol Biotechnol 59:9-14. 2002
    ..A novel reaction mechanism of PGA synthesis is proposed...
  23. ncbi Exploring 9-benzyl purines as inhibitors of glutamate racemase (MurI) in Gram-positive bacteria
    Bolin Geng
    AstraZeneca R and D Boston, Infection Discovery, 35 Gatehouse Drive, Waltham, MA 02451, USA
    Bioorg Med Chem Lett 18:4368-72. 2008
    ..X-ray co-crystal EI structures were obtained...
  24. ncbi Potent and selective inhibitors of Helicobacter pylori glutamate racemase (MurI): pyridodiazepine amines
    Bolin Geng
    AstraZeneca R and D Boston, Infection Discovery, 35 Gatehouse Drive, Waltham, MA 02451, USA
    Bioorg Med Chem Lett 19:930-6. 2009
    ..pylori activity, marked improved solubility, and reduced plasma protein binding. X-ray co-crystal E-I structures were obtained. These uncompetitive inhibitors bind at the MurI dimer interface...
  25. ncbi 4-Substituted D-glutamic acid analogues: the first potent inhibitors of glutamate racemase (MurI) enzyme with antibacterial activity
    Alfonso de Dios
    Eli Lilly and Co, Lilly S A, Avenida de la Industria, 30, 28108 Alcobendas, Madrid, Spain
    J Med Chem 45:4559-70. 2002
    ..Data described herein suggest that glutamate racemase may be a viable target for developing new antibacterial agents...
  26. ncbi Properties of glutamate racemase from Bacillus subtilis IFO 3336 producing poly-gamma-glutamate
    M Ashiuchi
    Research Institute of Molecular Genetics Kansai University, Suita, Osaka, 564 0073, Japan
    J Biochem 123:1156-63. 1998
    ..subtilis IFO 3336. These results suggest that the glutamate racemase is mainly concerned in D-glutamate synthesis for poly-gamma-glutamate production in B. subtilis IFO 3336...
  27. pmc Structural and functional analysis of two glutamate racemase isozymes from Bacillus anthracis and implications for inhibitor design
    Melissa May
    Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL 60607, USA
    J Mol Biol 371:1219-37. 2007
    ....
  28. ncbi Molecular cloning of a 25-kDa high affinity rapamycin binding protein, FKBP25
    Y J Jin
    Division of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
    J Biol Chem 267:10942-5. 1992
    ..These data demonstrate that FKBP25 has a higher affinity for rapamycin than for FK506 and suggest that this cellular receptor may be an important target molecule for immunosuppression by rapamycin...
  29. ncbi Mammalian l-to-d-amino-acid-residue isomerase from platypus venom
    Allan M Torres
    School of Molecular and Microbial Biosciences, University of Sydney, Building G08, Sydney, NSW 2006, Australia
    FEBS Lett 580:1587-91. 2006
    ..The isomerase is approximately 50-60 kDa and is inhibited by methanol and the peptidase inhibitor amastatin. This is the first known l-to-d-amino-acid-residue isomerase in a mammal...
  30. ncbi Protein folding in the cell
    M J Gething
    Department of Biochemistry, University of Texas Southwestern Medical Centre, Dallas 75235
    Nature 355:33-45. 1992
    ....
  31. ncbi The cyclophilin homolog ninaA is required in the secretory pathway
    N J Colley
    Howard Hughes Medical Institute University of California, San Diego, La Jolla 92093
    Cell 67:255-63. 1991
    ..These results are discussed in relation to the possible role of cyclophilins in protein folding and intracellular protein trafficking...
  32. ncbi Inhibition of DNA gyrase activity by Mycobacterium smegmatis MurI
    Sugopa Sengupta
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India
    FEMS Microbiol Lett 279:40-7. 2008
    ....
  33. pmc Isolation and characterization of a novel lysine racemase from a soil metagenomic library
    I Chien Chen
    Institute of Molecular Biology, College of Life Sciences, corrected National Chung Hsing University, Taichung, Taiwan
    Appl Environ Microbiol 75:5161-6. 2009
    ..7 kDa. The enzyme exhibited higher specific activity toward lysine in the l-lysine-to-d-lysine direction than in the reverse reaction...
  34. ncbi Exploitation of structural and regulatory diversity in glutamate racemases
    Tomas Lundqvist
    AstraZeneca Global Structural Chemistry, AstraZeneca R and D Molndal, SE 431 83, Molndal, Sweden
    Nature 447:817-22. 2007
    ..These structural, kinetic and mutational studies provide insight into the physiological regulation of these essential enzymes and provide a basis for designing narrow-spectrum antimicrobial agents...
  35. pmc Genetic immunization converts the trypanosoma cruzi B-Cell mitogen proline racemase to an effective immunogen
    Marianne A Bryan
    Department of Immunology, University of Pittsburgh School of Medicine, BST E1038, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Infect Immun 78:810-22. 2010
    ..Furthermore, coimmunization of TcPRAC with another T. cruzi antigen indicates the usefulness of this approach for multivalent vaccine development...
  36. ncbi Structure-stability-activity relationship in covalently cross-linked N-carbamoyl D-amino acid amidohydrolase and N-acylamino acid racemase
    Wei Chun Chiu
    Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, 30013, ROC
    J Mol Biol 359:741-53. 2006
    ..2-fold at 65 degrees C). Furthermore, molecular dynamic simulations reveal that A302C substantially sustains the fine-tuned catalytic site as temperature increases, achieving enhanced activity...
  37. pmc The murI gene of Escherichia coli is an essential gene that encodes a glutamate racemase activity
    P Doublet
    URA 1131 du Centre National de la Recherche Scientifique CNRS, Universite Paris Sud, Orsay, France
    J Bacteriol 175:2970-9. 1993
    ....
  38. ncbi Characterization of yrpC gene product of Bacillus subtilis IFO 3336 as glutamate racemase isozyme
    M Ashiuchi
    Research Institute of Molecular Genetics, Kochi University, Japan
    Biosci Biotechnol Biochem 63:792-8. 1999
    ..In addition, YrpC showed higher affinity and lower catalytic efficiency for L-glutamate than Glr. This is the first example showing the occurrence and properties of a glutamate racemase isozyme...
  39. pmc Biosynthesis of a D-amino acid in peptide linkage by an enzyme from frog skin secretions
    Alexander Jilek
    Institute of Molecular Biology, Austrian Academy of Sciences, Billrothstrasse 11, A 5020 Salzburg, Austria
    Proc Natl Acad Sci U S A 102:4235-9. 2005
    ..After expression of this cDNA in oocytes of Xenopus laevis, isomerase activity could be detected. Polypeptides related to the frog skin enzyme are present in several vertebrate species, including humans...
  40. ncbi Aslfm, the D-aspartate ligase responsible for the addition of D-aspartic acid onto the peptidoglycan precursor of Enterococcus faecium
    Samuel Bellais
    INSERM, U655 LRMA, Paris Cedex 06, France
    J Biol Chem 281:11586-94. 2006
    ..The Aslfm ligase appears as an attractive target for the development of narrow spectrum antibiotics active against multiresistant E. faecium...
  41. ncbi Biosynthetic alanine racemase of Salmonella typhimurium: purification and characterization of the enzyme encoded by the alr gene
    N Esaki
    Biochemistry 25:3261-7. 1986
    ..The inactivator-pyridoxal 5'-phosphate adduct was isolated and shown to be the same structure formed in the dadB racemase inactivation [Roise, D., Soda, K., Yagi, T., & Walsh, C. (1984) Biochemistry 23, 5195]...
  42. ncbi Differences in effects on DNA gyrase activity between two glutamate racemases of Bacillus subtilis, the poly-gamma-glutamate synthesis-linking Glr enzyme and the YrpC (MurI) isozyme
    Makoto Ashiuchi
    Department of Bioresources Science, Kochi University, Nankoku, Japan
    FEMS Microbiol Lett 223:221-5. 2003
    ..The YrpC isozyme, but not the Glr enzyme, was found to influence the activity of DNA gyrase, as did the MurI-type glutamate racemase of Escherichia coli, which is involved in peptidoglycan synthesis during cell division...
  43. ncbi Catalyzing racemizations in the absence of a cofactor: the reaction mechanism in proline racemase
    Amir Rubinstein
    Department of Chemistry and the Lise Meitner Minerva Center of Computational Quantum Chemistry, Bar Ilan University, Ramat Gan 52900, Israel
    J Am Chem Soc 131:8513-21. 2009
    ..This is ascribed to a highly preorganized active site facilitating transition state stabilization via a tight network of hydrogen bonds donated by nearby active site residues...
  44. ncbi UDP-N-acetylmuramyl-L-alanine functions as an activator in the regulation of the Escherichia coli glutamate racemase activity
    H T Ho
    Department of Microbiology, Bristol Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492
    Biochemistry 34:2464-70. 1995
    ..With 6.5 microM regulator added, the N-terminal truncated enzyme displayed a loss of more than 80% of the activity compared to the full-length enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)..
  45. ncbi Lysine racemase: a novel non-antibiotic selectable marker for plant transformation
    I Chieh Chen
    Institute of Molecular Biology, College of Life Sciences, National Chung Hsing University, Taichung, 402, Taiwan
    Plant Mol Biol 72:153-69. 2010
    ..To our knowledge, this is the first report to demonstrate that the lysine racemase selectable marker system is novel, less controversial and inexpensive than the traditional selection systems...
  46. ncbi Trypanosoma cruzi proline racemases are involved in parasite differentiation and infectivity
    Nathalie Chamond
    Department of Immunology, Institut Pasteur, CNRS, URA1961, Paris 75724, France
    Mol Microbiol 58:46-60. 2005
    ..These results strongly emphasize that TcPRAC is a potential target for drug design as well as for immunomodulation of parasite-induced B-cell polyclonal activation...
  47. ncbi Glr, a glutamate racemase, supplies D-glutamate to both peptidoglycan synthesis and poly-gamma-glutamate production in gamma-PGA-producing Bacillus subtilis
    Shigeki Kada
    Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo ku, 113 8657, Japan
    FEMS Microbiol Lett 236:13-20. 2004
    ..Phylogenetic analysis of glutamate racemases from eubacteria showed that YrpC is distinct from other glutamate racemases...
  48. ncbi D-amino acids in the brain: structure and function of pyridoxal phosphate-dependent amino acid racemases
    Tohru Yoshimura
    Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, Japan
    FEBS J 275:3527-37. 2008
    ..We compared the eukaryotic serine racemase with bacterial alanine racemase, the best-studied enzyme among the PLP-dependent amino acid racemases, and thus suggested a putative reaction mechanism for mammalian D-serine synthesis...
  49. ncbi Glutamate racemase is an endogenous DNA gyrase inhibitor
    Makoto Ashiuchi
    Department of Bioresources Science, Kochi University, Nankoku, Kochi 783 8502, Japan
    J Biol Chem 277:39070-3. 2002
    ..This is the first finding of the enzyme protein participating in both d-amino acid metabolism and DNA processing...
  50. ncbi Crystal structure of YHI9, the yeast member of the phenazine biosynthesis PhzF enzyme superfamily
    Dominique Liger
    Institut de Biochimie et de Biophysique Moléculaire et Cellulaire CNRS UMR 8619, Universite Paris Sud, Orsay, France
    Proteins 60:778-86. 2005
    ..Evolution of this protein by gene duplication, gene fusion and domain swapping from an ancestral gene containing the "hot dog" fold, identifies the protein as a "kinked double hot dog" fold...
  51. ncbi On the ionization state of the substrate in the active site of glutamate racemase. A QM/MM study about the importance of being zwitterionic
    Eduard Puig
    Departament de Quimica, Universitat Autonoma de Barcelona, Bellaterra Barcelona, Spain
    J Phys Chem A 110:717-25. 2006
    ..Importantly, the present theoretical results quantitatively support the mechanistic proposal by Rios et al. [J. Am. Chem. Soc. 2000, 122, 9373-9385] for the PLP-independent amino acid racemases...
  52. ncbi Polarimetric assay for the medium-throughput determination of alpha-amino acid racemase activity
    Dorian L Schönfeld
    Institute of Chemistry and Biochemistry, Department of Technical Chemistry and Biotechnology, Ernst Moritz Arndt University Greifswald, Soldmannstrasse 16, D 17487 Greifswald, Germany
    Anal Chem 76:1184-8. 2004
    ..Thus, the method described can be used to determine racemase activity in an automatic manner. It should be also applicable for the screening of enzyme libraries created by directed evolution...
  53. ncbi Synthesis of DL-tryptophan by modified broad specificity amino acid racemase from Pseudomonas putida IFO 12996
    Kuniki Kino
    Laboratory of Applied Biochemistry, Department of Applied Chemistry, School of Science and Engineering, Waseda University, 3 4 1 Okubo, Shinjuku ku, 169 8555, Tokyo, Japan
    Appl Microbiol Biotechnol 73:1299-305. 2007
    ..L-Trp (20 mM) was successfully racemized, and the proportion of D-Trp was reached 43% using I384M mutant BAR, while wild-type BAR racemized only 6% of initial L-Trp...
  54. pmc Crystal structure, catalytic mechanism, and mitogenic properties of Trypanosoma cruzi proline racemase
    Alejandro Buschiazzo
    Unité de Biochimie Structurale, Centre National de la Recherche Scientifique Institut Pasteur, 25 rue du Dr Roux, F 75724 Paris, France
    Proc Natl Acad Sci U S A 103:1705-10. 2006
    ....
  55. ncbi Compensation for D-glutamate auxotrophy of Escherichia coli WM335 by D-amino acid aminotransferase gene and regulation of murI expression
    L Liu
    Institute for Chemical Research, Kyoto University, Kyoto fu, Japan
    Biosci Biotechnol Biochem 62:193-5. 1998
    ..coli cells, as well as a regulation system for murI expression...
  56. ncbi Characterization and isolation of L-to-D-amino-acid-residue isomerase from platypus venom
    A M Torres
    School of Molecular and Microbial Biosciences, University of Sydney, Sydney, Australia
    Amino Acids 32:63-8. 2007
    ..Isolation of the isomerase was carried out by combined ion-exchange chromatography and reverse-phase high performance liquid chromatography (HPLC)...
  57. ncbi Mammalian peptide isomerase: platypus-type activity is present in mouse heart
    Jennifer M S Koh
    School of Molecular Biosciences, Building G08, University of Sydney, NSW 2006, Australia
    Chem Biodivers 7:1603-11. 2010
    ..Accordingly, eight mouse tissues were tested and heart was shown to have the activity. This is notable for being the first evidence of a peptide isomerase being present in a higher mammal and heralds finding the activity in man...
  58. ncbi Expression of glr (murI, dga) gene encoding glutamate racemase in Escherichia coli
    T Yoshimura
    Institute for Chemical Research, Kyoto University, Japan
    J Biol Chem 268:24242-6. 1993
    ..We partially purified the enzyme to characterize it. The enzyme consists of two identical subunits with a molecular weight of about 31,000 in contrast to the P. pentosaceus enzyme, a monomer protein...
  59. ncbi Proline racemases: insights into Trypanosoma cruzi peptides containing D-proline
    Nicolas Coatnoan
    Departement d Immunologie, Laboratoire d Immunobiologie des Infections à Trypanosoma, Institut Pasteur, Paris, France
    Mem Inst Oswaldo Cruz 104:295-300. 2009
    ..Our data suggest that D-proline-bearing peptides, similarly to the mucopeptide layer of bacterial cell walls, may be of benefit to T. cruzi by providing resistance against host proteolytic mechanisms...
  60. pmc Glutamate racemase from Mycobacterium tuberculosis inhibits DNA gyrase by affecting its DNA-binding
    Sugopa Sengupta
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, Karnataka, India
    Nucleic Acids Res 34:5567-76. 2006
    ..The sequestration of the gyrase by MurI results in inhibition of all reactions catalysed by DNA gyrase. MurI is thus not a typical potent inhibitor of DNA gyrase and instead its role could be in modulation of the gyrase activity...
  61. ncbi Expression, purification and preliminary X-ray analysis of crystals of Bacillus subtilis glutamate racemase
    Makie A Taal
    Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, England
    Acta Crystallogr D Biol Crystallogr 60:2031-4. 2004
    ..1 A resolution on a synchrotron-radiation source and are suitable for structural studies. Determination of the structure may provide insight into the molecular basis of substrate recognition and catalysis by this enzyme...
  62. ncbi Development of novel inhibitors targeting intracellular steps of peptidoglycan biosynthesis
    Miha Kotnik
    Lek Pharmaceuticals d d, Drug Discovery, Ljubljana, Slovenia
    Curr Pharm Des 13:2283-309. 2007
    ..Naturally occurring inhibitors and the development of low-molecular weight inhibitors of the intracellular part of peptidoglycan synthesis are presented...
  63. pmc Molecular and structural discrimination of proline racemase and hydroxyproline-2-epimerase from nosocomial and bacterial pathogens
    Maira Goytia
    Laboratoire d Immunobiologie des Infections à Trypanosoma, Departement d Immunologie, Institut Pasteur, Paris, France
    PLoS ONE 2:e885. 2007
    ....
  64. ncbi A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase
    B Reina-San-Martin
    Departement d Immunologie, CNRS URA 1960, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
    Nat Med 6:890-7. 2000
    ..This is the first report to our knowledge of a eukaryotic amino acid racemase gene. Our findings have potential consequences for the development of new immune therapies and drug design against pathogens...
  65. pmc A B lymphocyte mitogen is a Brucella abortus virulence factor required for persistent infection
    Juan Manuel Spera
    Instituto de Investigaciones Biotecnológicas Instituto Tecnológico Chascomús, Universidad Nacional de San Martin, Consejo Nacional de Investigaciones Cientificas y Tecnicas de Argentina, Avenida General Paz 5445, 1650 San Martin, Argentina
    Proc Natl Acad Sci U S A 103:16514-9. 2006
    ..We propose that an early and transient nonresponsive immune condition of the host mediated by this B cell polyclonal activator is required for establishing a successful chronic infection by Brucella...
  66. ncbi A novel ensemble-based scoring and search algorithm for protein redesign and its application to modify the substrate specificity of the gramicidin synthetase a phenylalanine adenylation enzyme
    Ryan H Lilien
    Computer Science Department, Dartmouth College, Hanover, NH 03755, USA
    J Comput Biol 12:740-61. 2005
    ..Our ensemble-based algorithm, which flexibly models both protein and ligand using rotamer-based partition functions, has application in enzyme redesign, the prediction of protein-ligand binding, and computer-aided drug design...
  67. pmc Structural insights into stereochemical inversion by diaminopimelate epimerase: an antibacterial drug target
    Bindu Pillai
    Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, AB, Canada T6G 2H7
    Proc Natl Acad Sci U S A 103:8668-73. 2006
    ..Bacterial racemases, including glutamate racemase and DAP epimerase, are potential targets for the development of new agents effective against organisms resistant to conventional antibiotics...
  68. ncbi Structure of aspartate racemase complexed with a dual substrate analogue, citric acid, and implications for the reaction mechanism
    Akashi Ohtaki
    Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184 8588, Japan
    Proteins 70:1167-74. 2008
    ..Based on the PhAspR-Cit complex structure, the reaction mechanism of aspartate racemase was elucidated...
  69. ncbi Crystal structure of aspartate racemase from Pyrococcus horikoshii OT3 and its implications for molecular mechanism of PLP-independent racemization
    Lijun Liu
    Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    J Mol Biol 319:479-89. 2002
    ....
  70. ncbi Roles of conserved basic amino acid residues and activation mechanism of the hyperthermophilic aspartate racemase at high temperature
    Takumitsu Yoshida
    Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo, Japan
    Proteins 64:502-12. 2006
    ..These results provide insights into the roles of amino acid residues at the catalytic site and also the activation mechanism of a hyperthermophilic aspartate racemase at high temperature...
  71. ncbi Statistical criteria for the identification of protein active sites using Theoretical Microscopic Titration Curves
    Jaeju Ko
    Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA
    Proteins 59:183-95. 2005
    ..The relationship between the statistical measures of nonsigmoidal behavior in the predicted titration curves and the catalytic activity of the residue is discussed...
  72. ncbi Prediction and assignment of function for a divergent N-succinyl amino acid racemase
    Ling Song
    Department of Biochemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    Nat Chem Biol 3:486-91. 2007
    ..These studies establish that ligand docking to a homology model can facilitate functional assignment of unknown proteins by restricting the identities of the possible substrates that must be experimentally tested...
  73. ncbi Structural basis for catalytic racemization and substrate specificity of an N-acylamino acid racemase homologue from Deinococcus radiodurans
    Wen Ching Wang
    Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 300, Taiwan, ROC
    J Mol Biol 342:155-69. 2004
    ..The other subsites involved in substrate recognition are less conserved, suggesting that divergent evolution has led to functionally distinct enzymes...
  74. ncbi Evolution of enzymatic activities in the enolase superfamily: structure of a substrate-liganded complex of the L-Ala-D/L-Glu epimerase from Bacillus subtilis
    Vadim A Klenchin
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 43:10370-8. 2004
    ..M., Hubbard, B. K., and Gerlt, J. A. (2001) Biochemistry 40, 15707-15715]. These studies provide important new information about the structural bases for substrate specificity in the enolase superfamily...
  75. ncbi Multiple substrate binding states and chiral recognition in cofactor-independent glutamate racemase: a molecular dynamics study
    Henrik Möbitz
    Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106, USA
    Biochemistry 43:9685-94. 2004
    ..We explain how the weak binding of Glu contributes to catalysis and suggest a mechanism by which binding mismatches are propagated into an opening of the active site...
  76. pmc Peptidyl-prolyl cis-trans-isomerase from Escherichia coli: a periplasmic homolog of cyclophilin that is not inhibited by cyclosporin A
    J Liu
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115
    Proc Natl Acad Sci U S A 87:4028-32. 1990
    ..By spheroplast fractionation of cells harboring the expression vector for the complete rot gene, the rotamase is located in the periplasm, where it could function in refolding of secreted proteins...
  77. ncbi Evolutionary potential of (beta/alpha)8-barrels: in vitro enhancement of a "new" reaction in the enolase superfamily
    Jacob E Vick
    Department of Biochemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    Biochemistry 44:11722-9. 2005
    ..These observations support our hypothesis that evolution of "new" functions in the enolase superfamily can occur simply by changes in specificity-determining residues...
  78. ncbi Molecular identification of monomeric aspartate racemase from Bifidobacterium bifidum
    Tatsuyuki Yamashita
    Department of Bioresources Science, Kochi University, Nankoku, Kochi, Japan
    Eur J Biochem 271:4798-803. 2004
    ..The recombinant enzyme was purified to homogeneity and its properties were almost the same as those of the B. bifidum enzyme...
  79. ncbi Refinement of Haemophilus influenzae diaminopimelic acid epimerase (DapF) at 1.75 A resolution suggests a mechanism for stereocontrol during catalysis
    Adrian John Lloyd
    Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, England
    Acta Crystallogr D Biol Crystallogr 60:397-400. 2004
    ..An analysis of the structure (i) in comparison to other PLP-independent racemaces and (ii) in relation to the catalytic mechanism and stereospecificity of DapF is presented...
  80. ncbi Mip protein of Legionella pneumophila exhibits peptidyl-prolyl-cis/trans isomerase (PPlase) activity
    G Fischer
    Max Planck Gesellschaft, Arbeitsgruppe Enzymologie der Peptidbindung, Halle, Germany
    Mol Microbiol 6:1375-83. 1992
    ..In view of the activity of PPIases in protein-folding reactions, such prokaryotic FKBP analogues may represent a new class of bacterial pathogenicity factors...
  81. ncbi Structure of the amino-terminal core domain of the HIV-1 capsid protein
    R K Gitti
    Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD 21228, USA
    Science 273:231-5. 1996
    ..In the free monomeric domain, Pro90 adopts kinetically trapped cis and trans conformations, raising the possibility that cyclophilin A catalyzes interconversion of the cis- and trans-Pro90 loop structures...
  82. ncbi The substrate-binding site in Escherichia coli cyclophilin A preferably recognizes a cis-proline isomer or a highly distorted form of the trans isomer
    M Konno
    Department of Chemistry, Faculty of Science Ochanomizu University, Tokyo, Japan
    J Mol Biol 256:897-908. 1996
    ..coli CyPA forming a complex with CsA. Thus, the extra amino acid residue of E. coli CyPA, polar Gln89, lies along the pathway to the hydrophobic pocket of CyPA and seems to prevent the access hydrophobic part of CsA to the cleft of CyPA...
  83. pmc Crystal structure of murine cyclophilin C complexed with immunosuppressive drug cyclosporin A
    H Ke
    Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill 27599
    Proc Natl Acad Sci U S A 90:11850-4. 1993
    ..Alternatively, the previous CyPA-CsA structure at low resolution may not provide sufficient details for a comparison with the CyPC-CsA structure...
  84. ncbi X-ray structure of a monomeric cyclophilin A-cyclosporin A crystal complex at 2.1 A resolution
    V Mikol
    Preclinical Research, Sandoz AG, Basel, Switzerland
    J Mol Biol 234:1119-30. 1993
    ..The fact that this monomeric crystal form can be obtained shows that the formation of pentamer or decamer complexes is not a generally observed phenomenon and is not a prerequisite for biological activity...
  85. pmc X-ray structure of a cyclophilin B/cyclosporin complex: comparison with cyclophilin A and delineation of its calcineurin-binding domain
    V Mikol
    Preclinical Research, Sandoz AG, Basel, Switzerland
    Proc Natl Acad Sci U S A 91:5183-6. 1994
    ..The three residues Arg90, Lys113, and Ala128 and the loop containing Arg158 on the surface of CypB are likely to modulate the differences in calcineurin inhibition between CypA and CypB...
  86. pmc Yeast NPI46 encodes a novel prolyl cis-trans isomerase that is located in the nucleolus
    X Shan
    Department of Biological Sciences, Columbia University, New York 10027
    J Cell Biol 126:853-62. 1994
    ..By indirect immunofluorescence we have shown that NPI46 is a nucleolar protein. NPI46 is not essential for cell viability...
  87. ncbi Human cyclophilin C: primary structure, tissue distribution, and determination of binding specificity for cyclosporins
    H Schneider
    Sandoz Pharma Ltd, Basel, Switzerland
    Biochemistry 33:8218-24. 1994
    ..The knowledge of the fine specificity of human Cyps for CsA and of their expression levels may provide better insights into how CsA acts on its different target proteins in vivo...
  88. pmc The characterization of a cyclophilin-type peptidyl prolyl cis-trans-isomerase from the endoplasmic-reticulum lumen
    S Bose
    Research School of Biosciences, Biological Laboratory, University of Kent, Canterbury, U K
    Biochem J 300:871-5. 1994
    ..Kinetic properties, substrate-specificity data and inhibition by cyclosporin A indicate that it is a cyclophilin-type PPI, consistent with the amino-acid-sequence results...
  89. pmc A ribosome-associated peptidyl-prolyl cis/trans isomerase identified as the trigger factor
    G Stoller
    Max Planck Gesellschaft, Arbeitsgruppe Enzymologie der Peptidbindung, Berlin, Germany
    EMBO J 14:4939-48. 1995
    ..In vitro, the trigger factor catalysed the proline-limited refolding of a variant of RNase T1 much better than all other PPIases that have been examined so far...
  90. ncbi Characterization of Mip proteins of Legionella pneumophila
    B Ludwig
    Institut für Molekulare Infektionsbiologie, Univ Würzburg, FRG
    FEMS Microbiol Lett 118:23-30. 1994
    ..The mature Mip proteins exist in an oligomeric form. Site-directed mutagenesis demonstrated that a substitution of an Asp residue at position 142 by a Leu residue affects PPIase activity of Mip...
  91. pmc Crystal structure of recombinant human T-cell cyclophilin A at 2.5 A resolution
    H M Ke
    Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599
    Proc Natl Acad Sci U S A 88:9483-7. 1991
    ..Inside the barrel, seven aromatic and other hydrophobic residues form a compact hydrophobic core. A loop of Lys-118 to His-126 and four beta-strands (B3-B6) constitute a pocket we speculate to be the binding site of cyclosporin A...
  92. ncbi Structure of human cyclophilin and its binding site for cyclosporin A determined by X-ray crystallography and NMR spectroscopy
    J Kallen
    Preclinical Research, Sandoz Pharma AG, Basel, Switzerland
    Nature 353:276-9. 1991
    ..These results may help to provide a structural basis for rationalizing the immunosuppressive function of the cyclosporin-cyclophilin system and will also be important in the design of improved immunosuppressant drugs...
  93. ncbi Glutamate mutase from Clostridium cochlearium. Purification, cobamide content and stereospecific inhibitors
    U Leutbecher
    Laboratorium für Mikrobiologie, Fachbereich Biologie, Philipps Universitat, Marburg, Federal Republic of Germany
    Eur J Biochem 205:759-65. 1992
    ..However, the presence of an N-terminal pyruvoyl residue was excluded and no evidence for the participation of another electrophilic center in the reaction was obtained...
  94. ncbi Genetic dissection of cyclophilin function. Saturation mutagenesis of the Drosophila cyclophilin homolog ninaA
    B Ondek
    Howard Hughes Medical Institute, La Jolla, California
    J Biol Chem 267:16460-6. 1992
    ..We also show that mammalian cyclophilins engineered to contain missense mutations found in two temperature-sensitive ninaA alleles display temperature-sensitive prolyl cis/trans isomerase activity...
  95. ncbi Structural and functional characterization of Escherichia coli peptidyl-prolyl cis-trans isomerases
    L A Compton
    Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland
    Eur J Biochem 206:927-34. 1992
    ..Circular dichroism spectroscopy indicates that the secondary structure of the cationic protein consists of 17% alpha-helix, 34% beta-sheet, 17% turns, 33% random coil and is very similar to human cytosolic PPIase...
  96. ncbi Isolation and amino acid sequence of a new 22-kDa FKBP-like peptidyl-prolyl cis/trans-isomerase of Escherichia coli. Similarity to Mip-like proteins of pathogenic bacteria
    J U Rahfeld
    Max Planck Gesellschaft, Arbeitsgruppe Enzymologie der Peptidbindung, Kurt Mothes Strasse 3, D 06120 Halle Saale, Germany
    J Biol Chem 271:22130-8. 1996
    ..The subsite specificity regarding the P1 position of the substrate resembles that for Mip-FKBP25 from Legionella pneumophila. The mature FKBP22 enzyme of 205 amino acids exists as a dimer in solution...
  97. ncbi Extended binding sites of cyclophilin as revealed by the interaction with HIV-1 Gag polyprotein derived oligopeptides
    M Schutkowski
    Max Planck Gesellschaft zur Förderung der Wissenschaften e V, Arbeitsgruppe Enzymologie der Peptidbindung, Halle Saale, Germany
    FEBS Lett 394:289-94. 1996
    ....
  98. ncbi Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent
    R Ranganathan
    Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Cell 89:875-86. 1997
    ..This raises the possibility of phosphorylation-mediated control of Pin1-substrate interactions in cell cycle regulation...
  99. ncbi Dynamics of catalysis revealed from the crystal structures of mutants of diaminopimelate epimerase
    Bindu Pillai
    Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alta, Canada T6G 2H7
    Biochem Biophys Res Commun 363:547-53. 2007
    ..This structural rearrangement is critical for catalysis...
  100. ncbi The V3 loop of human immunodeficiency virus type-1 envelope protein is a high-affinity ligand for immunophilins present in human blood
    M M Endrich
    Biochemisches Institut, Universitat Zurich, Switzerland
    Eur J Biochem 252:441-6. 1998
    ....
  101. ncbi Functional analysis of the yeast 40 kDa cyclophilin Cyp40 and its role for viability and steroid receptor regulation
    R Warth
    Departement de Biologie Cellulaire, Universite de Geneve, Switzerland
    Biol Chem 378:381-91. 1997
    ..While other immunophilins could conceivably compensate a Cyp40 defect, our results are compatible with the notion that immunophilins may be fortuitous partners in the biochemically established steroid receptor-Hsp90 complex...

Research Grants5

  1. COMPLEMENT REGULATION IN TRYPANOSOMA CRUZI
    Karen Norris; Fiscal Year: 2005
    ..The successful completion of these aims will provide the first functional and immunological evaluation of a critical virulence factor of T. cruzi and provide information and reagents for the use of CRP as a vaccine candidate. ..
  2. PNEUMOCYSTIS CARINII PNEUMONIA MODEL IN RHESUS MACAQUES
    Karen Norris; Fiscal Year: 2002
    ..carinii and determine the relevance of the nonhuman primate model, thus providing the means to study many aspects of PCP previously unapproachable due to the limitations of other animal models. ..
  3. T. cruzi immune evasion factors and vaccine design
    Karen Norris; Fiscal Year: 2008
    ..No vaccine is currently available to prevent or treat Chagas' disease and the proposed studies will test two vaccine candidates in experimental models. [unreadable] [unreadable] [unreadable]..
  4. Immune response to Pneumocystis in simian model of AIDS
    Karen Norris; Fiscal Year: 2009
    ....
  5. Pneumocystis and COPD in a Simian Model of AIDS
    Karen Norris; Fiscal Year: 2009
    ..abstract_text> ..