Faculty Information, Institute for Chemical Research, Kyoto University   [ English | Japanese ]


HIRATAKE, Jun

Division of Biochemistry - Chemistry of Molecular Biocatalysts -
（Laboratory in the Graduate School of Agriculture, Kyoto University）
Professor
Doctor of Agricultural Science
URL:http://www.scl.kyoto-u.ac.jp/~hiratake/index-j.html
E-mail: hiratake@scl.kyoto-u.ac.jp
Tel: +81-774-38-3231
Fax: +81-774-38-3229
Academic career
    1985.3 Graduated from Master Course, Kyoto University (Graduate School of Agriculture)
    1987.8-1996.7 Instructor, Institute for Chemical Research, Kyoto University
    1989.7 Doctoral Degree of Agricultural Science, Kyoto University
    1989.7-1991.1 Postdoctoral Fellow, University of Illinois at Chicago
    1996.8-2008.9.30 Associate Professor, Institute for Chemical Research, Kyoto University
    2008.10.1- Professor, Institute for Chemical Research, Kyoto University
Research field
    Bioorganic Chemistry, Enzyme Chemistry, Synthetic Organic Chemistry
Current research
  1. Rational Design and Synthesis of Specific Inhibitors of γ-Glutamyl Transpeptidase and Their Applications
  2. Synthesis and Evaluation of Specific Inhibitors of γ-Glutamyltcysteine Synthetase As Drug Seeds
  3. Derivatization of Transition-state Analog Inhibitors of Asparagine Synthetase for Development of Chemotherapeutic Agents for Asparaginase-resistant Leukemia and Cancer
  4. Mechanism of Plant hormone homeostasis Probed by Enzyme Inhibitors
Selected publications
  1. Hiratake J, Yamamoto Y, Oda J, Catalytic Asymmetric Induction from Prochiral Cyclic Acid Anhydrides using Cinchona Alkaloids J. Chem. Soc., Chem. Commun. , 1717-1719 (1985)
  2. Hiratake J, Inagaki M, Yamamoto Y, Oda J, Enantiotopic-group Differentiation.Catalytic Asymmetric Ring-opening of Prochiral Cyclic Acid Anhydrides with Methanol, using CinchonaAlkaloids J. Chem. Soc. Perkin Trans. I , 1053-1058 (1987)
  3. Inagaki M, Hiratake J, Yamamoto Y, Oda J, Asymmetric Induction in the Base-Catalyzed Reactions Using Polymer-Supported Quinines with SpacerGroups Bull. Chem. Soc. Jpn. 60, 4121-4126 (1987)
  4. Hiratake J, Shibata K, Baba N, Oda J, Enantiotopic-Group Differentiation.Asymmetric Monoesterification of Malonic Acids Using Cinchona Alkaloid Derivatives Synthesis , 278-280 (1988)
  5. Baba N, Mimura M, Hiratake J, Uchida K, Oda J, Enzymatic Resolution of Racemic Hydroperoxides in OrganicSolvent Agric. Biol. Chem. 52, 2685-2687 (1988)
  6. Hiratake J, Inagaki M, Nishioka T, Oda J, Irreversible and Highly Enantioselective Acylation of 2-Halo-1-arylethanols in Organic Solvents Catalyzed by a Lipase from Pseudomonas fluorescens J. Org. Chem. 53, 6130-6133 (1988)
  7. Nishio T, Tanaka N, Hiratake J, Katsube Y, Ishida Y, Oda J, Isolation and Structure of the Novel Dihydroxamate Siderophore Alcaligin J. Am. Chem. Soc. 110, 8733-8734 (1988)
  8. Hiratake J, Yamamoto K, Yamamoto Y, Oda J, Highly Regioselective Ring-Opening of α-Substituted Cyclic Acid Anhydrides Catalyzed by Lipase Tetrahedron Lett. 30, 1555-1556 (1989)
  9. Inagaki M, Hiratake J, Nishioka T, Oda J, Lipase-catalyzed Stereoselective Acylation of [1,1'-Binaphthyl]-2,2'-diol and Deacylation of Its Esters in an OrganicSolvent Agric. Biol. Chem. 53, 1879-1884 (1989)
  10. Moriarty RM, Hiratake J, Liu K, New Synthetic Route to Unsymmetrically Substituted Pentacoordinated Phosphorus. Hydrolytically Stable Chiral Monocyclic Oxyphosphoranes J. Am. Chem. Soc. 112, 8575-8577 (1990)
  11. Inagaki M, Hiratake J, Nishioka T, Oda J, Lipase-Catalyzed Kinetic Resolution with in Situ Racemization: One-Pot Synthesis of Optically Active Cyanohydrin Acetates fromAldehydes J. Am. Chem. Soc. 113, 9360-9361 (1991)
  12. Moriarty RM, Hiratake J, Liu K, Wendler A, Awasthi AK, Gilardi R, Isolation and Characterization of Stereoisomers of Pentacoordinated Phosphorus. Hydrolysis of Unsymmetrically Substituted Chiral Monocyclic Oxyphosphoranes J. Am. Chem. Soc. 113, 9374-9376 (1991)
  13. Nishioka T, Chihara-Shiomi M, Yoshikawa Y, Inagaki M, Yamamoto Y, Hiratake J, Baba N, Oda J, Lipase from Pseudomonas sp.: Reactions, Cloning, and Amino Acid Sequence Analysis Lipases: Structure, Mechanism and Genetic Engineering, GBF Monographs Vol. 16, ed. by Alberghia L, Schmid RD, Verger L; VCH, Weinheim , pp. 253-262 (1991)
  14. Inagaki M, Hatanaka A, Mimura M, Hiratake J, Nishioka T, Oda J, One-Pot Synthesis of Optically Active Cyanohydrin Acetates from Aldehydes via Quinidine-Catalyzed Transhydrocyanation Coupled with Lipase-Catalyzed Kinetic Resolution in OrganicSolvent Bull. Chem. Soc. Jpn. 65, 111-120 (1992)
  15. Nakatani T, Hiratake J, Yoshikawa K, Nishioka T, Oda J, Chemical Inactivation of Lipase in Organic Solvent: A Lipase from Pseudomonas aeruginosa TE3285 is More Like a Typical Serine Enzyme in an Organic Solvent than in AqueousMedia Biosci. Biotech. Biochem. 56, 1118-1123 (1992)
  16. Inagaki M, Hiratake J, Nishioka T, Oda J, One-Pot Synthesis of Optically Active Cyanohydrin Acetates from Aldehydes via Lipase-Catalyzed Kinetic Resolution Coupled with in Situ Formation and Racemization ofCyanohydrins J. Org. Chem. 57, 5643-5649 (1992)
  17. Nakatani T, Hiratake J, Shinzaki A, Umeshita R, Suzuki T, Nishioka T, Nakajima H, Oda J, A Mode of Product Inhibition of an Esterolytic Antibody Tetrahedron Lett. 34, 4945-4948 (1993)
  18. Oda J, Nakatani T, Hiratake J, Catalytic antibodies and multiple turnovers-- a "substrate tuning" for relieving catalytic antibody of product inhibition New Funtionality Materials, vol. C: Synthetic Process and Control of Functionality Materials, ed. by Tsuruta T, Doyama M, Seno M; Elsevier, Amsterdam , pp. 561-564 (1993)
  19. Inagaki M, Hiratake J, Nishioka T, Oda J, One-pot Conversion of Aldehydes to (S)-2-Acetoxy Nitriles via Reversible CyanohydrinFormation Preparative Biotransformations, 2nd supplement, John Wiley & Sons , pp. 1:10:30-39 (1993)
  20. Nakatani T, Umeshita R, Hiratake J, Shinzaki A, Suzuki T, Nakajima H, Oda J, Characterization of a Catalytic Antibody for Stereoselective Ester Hydrolysis—A Catalytic Residue and Mode of ProductInhibition Bioorg. Med. Chem. 2, 457-468 (1994)
  21. Hiratake J, Kato H, OdaJ, Mechanism-Based Inactivation of Glutathione Synthetase by Phosphinic Acid Transition-State Analogue J. Am. Chem. Soc. 116, 12059-12060 (1994)
  22. Katoh M, Hiratake J, Kato H, Oda J, Mechanism-Based Inactivation of E. coli gamma-Glutamylcysteine Synthetase by Phosphinic Acid- and Sulfoximine-Based Transition-State Analogues Bioorg. Med. Chem. Lett. 6, 1437-1442 (1996)
  23. Hiratake J, Oda J, Aminophosphonic and Aminoboronic Acids As a Key Element of Transition-State Analogue Inhibitor of Enzymes Biosci. Biotech. Biochem. 61, 211-218 (1997)
  24. Sawa M, Imaeda Y, Hiratake J, Fujii R, Umeshita R, Watanabe M, Kondo H, Oda J, Toward the Antibody-Catalyzed Chemiluminescence. Design and Synthesis of Hapten Bioorg. Med. Chem. Lett. 8, 647-652 (1998)
  25. Katoh M, Hiratake J, Oda J, ATP-Dependent Inactivation of E. coli gamma-Glutamylcysteine Synthetase by L-Glutamic Acid gamma-Monohydroxamate Biosci. Biotech. Biochem. 62, 1455-1457 (1998)
  26. Tokutake N, Hiratake J, Katoh M, Irie T, Kato H, Oda J, Design, Synthesis and Evaluation of Transition-State Analogue Inhibitors of Escherichia coli gamma-Glutamylcysteine Synthetase Bioorg. Med. Chem. 6, 1935-1953 (1998)
  27. Tokutake N, Hiratake J, Irie T,Yamano A, OdaJ, Absolute Configuration of an Intermediate Cyclic Sulfoximine in the Asymmetric Synthesis of Transition-State Analogue Inhibitors of gamma-GlutamylcysteineSynthetase Acta Crystallogr. C55, 1598-1599 (1999)
  28. Koizumi M, Hiratake J, Nakatsu T, Kato H, Oda J, A Potent Transition-State Analogue Inhibitor of Escherichia coli Asparagine Synthetase A J. Am. Chem. Soc. 121, 5799-5800 (1999)
  29. Inoue M, Hiratake J, Sakata K, Synthesis and Characterization of Intermediate and Transition-state Analogue Inhibitors of gamma-Glutamyl Peptide Ligases Biosci. Biotechnol. Biochem. 63, 2248-2251 (1999)
  30. Inoue M, Hiratake J, Suzuki H, Kumagai H, Sakata K, Identification of Catalytic Nucleophile of E. coli gamma-Glutamyltranspeptidase by gamma-Monofluorophosphono Derivative of Glutamic Acid: N-Terminal Thr-391 in Small Subunit is the Nucleophile Biochemistry 39, 7764-7771 (2000)
  31. Guo W, Hiratake J, Ogawa K, Yamamoto M, Ma S-J, Sakata K, beta-Glycosylamidines: Potent, Selective, and Easily Accessible beta-Glycosidase Inhibitors Bioorg. Med. Chem. Lett. 11, 467-470 (2001)
  32. Boehlein SK, Nakatsu T, Hiratake J, Thirumoorthy R, Stewart JD, Richards NGJ, Schuster SM, Characterization of Inhibitors Acting at the Synthetase Site of Escherichia coli Asparagine Synthetase B Biochemistry 40, 11168-11175 (2001)
  33. Ma S-J, Hiratake J, Nakai Y, Izumi M, Fukase K, Kusumoto S, Sakata K, A Direct Continuous Spectrophotometric Assay for Glycosidases with 3-Nitro2-pyridyl Glycosides by Tautomerization of 2-Hydroxy-3-nitropyridine Anal. Biochem. 302, 291-297 (2002)
  34. Hiratake J, Inoue M, Sakata K, gamma-Glutamyltranspeptidase and gamma-Glutamyl Peptide Ligases: Use of Fluorophosphonate and Phosphonodifluoromethyl Ketone Analogues as Probes of the Tetrahedral Transition State and the gamma-Glutamyl-P Intermediate Methods in Enzymology 354, 272-295 (2002)
  35. Hiratake J, Irie T, Tokutake N, Oda J, Recognition of a Cysteine Substrate by E. coli　gamma-Glutamylcysteine Synthetase Probed by Sulfoximine-Based Transition-state Analogue Inhibitors Biosci. Biotechnol. Biochem. 66, 1500-1514 (2002)
  36. Hiratake J, Suzuki H, Kumagai H, γ-Glutamyl transpeptidase and Its Precursor Handbook of Proteolytic Enzymes, 2nd edition, ed. by Barrett AJ, Rawlings ND, Woessner JF; Academic Press, Oxford (2004), pp. 2090-2094
  37. Hiratake J, Rational Design and Synthesis of Enzyme Inhibitors: Significance in Probing the Function of Enzymes J. of Synthetic Organic Chemistry, Special Issue in English 60, 1095-1103 (2002)
  38. Fujii R, Utsunomiya Y, Hiratake J, Sogabe A, Sakata K, Highly Sensitive Active-site Titration of Lipase in Microscale Culture Media Using Fluorescent Organophosphorus Ester Biochim. Biophys. Acta (Molecular and Cell Biology of Lipids) 1631, 197-205 (2003)
  39. Hiratake J, Sakata K, Glycosylamidines as Potent Selective and Easily Accessible Glycosidase Inhibitors and Their Application to Affinity Chromatography Methods in Enzymology 363, 421-444 (2003)
  40. Inoue K, Hiratake J, Mizutani M, Takada M, Yamamoto M, Sakata K, β-Glycosylamidine as Ligand for Affinity Chromatography Tailored to Glycon Substrate Specificity of β-Glycosidases Carbohydr. Res. 338, 1477-1491 (2003)
  41. Hibi T, Nii H, Nakatsu T, Kimura A, Kato H, Hiratake J and Oda J, Crystal structure of gamma-glutamylcysteine synthetase: Insights into the mechanism of catalysis by a key enzyme for glutathione homeostasis Proc. Natl. Acad. Sci. USA 101, 15052-15057 (2004).
  42. Kato M, Uno T, Hiratake J, Sakata K, alpha-Glucopyranoimidazolines as intermediate analogue inhibitors of family 20 beta-N-acetylglucosaminidases Bioorg. Med. Chem. 13, 1563-1571 (2005).
  43. Fujii R, Nakagawa Y, Hiratake J, Sogabe A, Sakata K, Directed evolution of Pseudomonas aeruginosa lipase for improved amide-hydrolyzing activity Protein Engineering, Design and Selection 18, 93-101 (2005).
  44. Hiratake J, Enzyme Inhibitors as Chemical Tools to Study Enzyme Catalysis: Rational Design, Synthesis, and Applications The Chemical Record 5, 209-228 (2005).
  45. Fujita K, Oura F, Nagamine N, Katayama T, Hiratake J, Sakata K, Kumagai H, Yamamoto K, Identification and molecular cloning of a novel glycoside hydrolase family of core 1 type O-glycan-specific endo-alfa-N-acetylgalactosaminidase from Bifidobacterium longum J. Biol. Chem. 280, 37415-37422 (2005).
  46. Nakatsu T, Ichiyama S, Hiratake J, Saldanha A, Kobayashi, N, Sakata K, Kato H, Structural basis for spectral difference in luciferase bioluminescence Nature 440, 372-376 (2006).
  47. Han L, Hiratake J, Tachi N, Suzuki H, Kumagai H, Sakata K, γ-(Monophenyl)phosphono glutamate analogues as mechanism-based inhibitors of γ-glutamyl transpeptidase Bioorg. Med. Chem. 14, 6043-6054 (2006).
  48. Tomiya N, Narang, S, Park, J, Abdul-Rahman, B, Choi O, Singh S, Hiratake J, Sakata K, Betenbaugh MJ, Palter KB, Lee YC, Purification, characterization, and cloning of a Spodoptera frugiperda SF9 beta-N-acetylhexosaminidase that hydrolyzes terminal N-acetylglucosamine on N-glycan core J. Biol. Chem. 281, 19545-19560 (2006).  [pubmed]
  49. Han L, Hiratake J, Kamiyama A, Sakata K, Design, Synthesis and Evaluation of gamma-Phosphono Diester Analogues of Glutamate as Highly Potent Inhibitors and Active Site Probes of gamma-Glutamyl Transpeptidase Biochemistry 46, 1432-1447 (2007).
  50. Guitierrez JA, Pan Y.-X, Koroniak L. Hiratake J, Kilberg MS, Richards NGJ, An Inhibitor of Human Asparagine Synthetase Suppresses Proliferation of an L-Asparaginase Resistant Leukemia Cell Line Chem. Biol. 13, 1339-1347 (2006).
  51. Hiratake J, β-Glycosylamidines as Inhibitors of β-Glycosidases and Their Use as Ligand for Affinity Chromatography Trends in Glycosci. Glycotechnol. 18, 371-381 (2006).
  52. Nakagawa Y, Hasegawa A, Hiratake J*, Sakata K, Engineering of Pseudomonas aeruginosa lipase by directed evolution for enhanced amidase activity: mechanistic implication for amide hydrolysis by serine hydrolases Protein Engineering, Design and Selection 20, 339-346 (2007).
  53. Wada K, Hiratake J, Irie M, Okada T, Yamada C, Kumagai H, Suzuki H, Fukuyama K, Crystal Structures of Escherichia coli gamma-Glutamyltranspeptidase in Complex with Azaserine and Acivicin: Novel Mechanistic Implication for Inhibition by Glutamine Antagonists J.Mol. Biol. 380, 361-372 (2008).
  54. Ikeuchi, Y.; Meyer, M. E.; Ding, Y.; Hiratake, J.; Richards, N. G. J., A Critical Electrostatic Interaction Mediates Inhibitor Recognition by Human Asparagine Synthetase Bioorg. Med. Chem. 17, 6641-6650 (2009)
  55. Ogata, M.; Kameshima, Y.; Hattori, T.; Michishita, K.; Suzuki, T.; Kawagishi, H.; Totani, K.; Hiratake, J.; Usui, T., Lactosylamidine-Based Affinity Purification for Cellulolytic Enzymes EG I and CBH I from Hypocrea jecorina and Their Properties Carbohydr. Res. 345, 2623-2329 (2010)
  56. Joyce-Brady, M.; Hiratake, J., Inhibiting Glutathione Metabolism in Lung Lining Fluid as a Strategy to Augment Antioxidant Defense Curr. Enz. Inhibit. 7, 71-78 (2011)
  57. Hiratake, J.; Suzuki, H.; Fukuyama, K.; Wada, K.; Kumagai, H., γ-Glutamyltranspeptidase and Its Precursor Handbook of Proteolytic Enzymes, 3rd Ed. Chapter 820, 3712-3719 (2013)
  58. Yamamoto, S.; Watanabe, B.; Hiratake, J.; Tanaka, R.; Ohkita, M.; Matsumura, Y., Preventive Effect of GGsTop, a Novel and Selective γ-Glutamyl Transpeptidase Inhibitor, on Ischemia/Reperfusion-Induced Renal Injury in Rats J. Pharmacol. Exp. Therapeutics 339, 945-951 (2011)
  59. Koeduka, T.; Watanabe, B.; Suzuki, S.; Hiratake, J.; Mano, J.; Yazaki, K., Characterization of Raspberry Ketone/Zingerone Synthase, Catalyzing the α, β-Hydrogenation of Phenylbutanones in Raspberry Fruits Biochem. Biophys. Res. Commun. 412, 104-108 (2011)
  60. Sato, S.; Kawamoto, J.; Sato, B. S.; Watanabe, B.; Hiratake, J.; Esaki, N.; Kurihara, T., Occurrence of Bacterial Membrane Microdomain at the Cell Division Site Enriched in Phospholipids with Polyunsaturated Hydrocarbon Chain J. Biol. Chem. 287, 24113-24121 (2012)
  61. Ikeuchi, H.; Ahn, Yong-Mo; Otokawa, T.; Watanabe, B.; Hegazy, L.; Hiratake, J.*; Richards, Nigel, G. J. , A Sulfoximine-Based Inhibitor of Human Asparagine Synthetase Kills L-Aspraginase-Resistant Leukemia Cells Bioorg. Med. Chem. 20, 5915-5927 (2012)

Update: May 16,2013