Crystal structures of penicillin binding proteins from Haemophilus influenzae

• Project/Area Number: 19570109
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Yokohama City University
• Principal Investigator: PARK Sam-yong Yokohama City University, 生命ナノシステム科学研究科, 准教授 (20291932)
• Co-Investigator(Kenkyū-buntansha): JEREMY Tame (JEREMY R.H.Tame / JEREMY R.H. Tame) 横浜市立大学, 生命ナノシステム科学研究科, 教授 (00336588) ; UNZAI Satoru 横浜市立大学, 生命ナノシステム科学研究科, 助教 (60336592)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 構造生物学 / 抗生物質開発

Research Abstract

細菌の細胞壁は、浸透圧や外界からの物理的損傷から自身を守り、成長や分裂時には盛んに生合成される組織の1つである。ペニシリンを代表とするβ-ラクタム系抗生物質は、もっとも古くから使用されてきた1つであり、主にグラム陰性菌に対して非常に有効で、現在も、最も多く使用されている抗菌剤である。本研究の目的は、インフルエンザ菌由来のPBPsの立体構造を解明し、新たなインフルエンザ菌の新抗生剤開発を行う予定である。

Research Products

• [Journal Article] A Common Mechanism for the ATP-DnaA-dependent Formation of Open Complexes at the Replication Origin (2008)
  • Author(s): Ozaki S, Kawakami H, Nakamura K, Fujikawa N, Kagawa W, Park SY, Yokoyama S, Kurumizaka H, Katayama T
  • Journal Title: J Biol Chem. 283(13) Pages: 8351-62
• [Journal Article] Crystal structures of the clock protein EA4 from the silkworm Bombyx mori (2008)
  • Author(s): Hiraki T, Shibayama N, Akashi S, Park SY
  • Journal Title: J Mol Biol. 377(3) Pages: 630-5
• [Journal Article] The structural basis for an essential subunit interaction in influenza virus RNA polymerase (2008)
  • Author(s): Obayashi E, Yoshida H, Kawai F, Shibayama N, Kawaguchi A, Nagata K, Tame JR, Park SY
  • Journal Title: Nature. 454(7208) Pages: 1127-31
  • NAID: 10023987774
• [Journal Article] The structural basis for an essential subunit interaction in influenza virus RNA polymerase. (2008)
  • Author(s): Obayashi E, et al
  • Journal Title: Nature 454 Pages: 1127-31
  • Peer Reviewed
• [Journal Article] Crystal structures of the clock protein EA4 from the silkworm Bombyx mori. (2008)
  • Author(s): Hiraki T, et al
  • Journal Title: J Mol Biol. 377 Pages: 630-5
  • Peer Reviewed
• [Journal Article] A Common Mechanism for the ATP-DnaA-dependent Formation of Open Complexes at the Replication Origin. (2008)
  • Author(s): Ozaki s, et al
  • Journal Title: J Biol Chem. 283 Pages: 8351-62
  • Peer Reviewed
• [Journal Article] Intersubunit linker length as a modifier of protein stability: crystal structures and thermostability of mutant TRAP. (2008)
  • Author(s): Watanabe M, Mishima Y, Yamashita I, Park SY, Tame JR, Heddle JG.
  • Journal Title: Protein Sci. 17(3) Pages: 518-26
  • Peer Reviewed
• [Journal Article] Structure and mechanism of HpcG, a hydratase in the homoprotocatechuate degradation pathway of Escherichia coli (2007)
  • Author(s): Izumi A, Rea D, Adachi T, Unzai S, Park SY, Roper DI, Tame JR
  • Journal Title: J Mol Biol. 370(5) Pages: 899-911
• [Journal Article] Dynamic allostery in the ring protein TRAP (2007)
  • Author(s): Heddle JG, Okajima T, Scott DJ, Akashi S, Park SY, Tame JR
  • Journal Title: J Mol Biol. 371(1) Pages: 154-67
• [Journal Article] Protonation States of Buried Histidine Residues in Human Deoxyhemoglobin Revealed by Neutron Crystallography (2007)
  • Author(s): Chatake T, Shibayama N, Park SY, Kurihara K, Tamada T, Tanaka I, Niimura N, Kuroki R, Morimoto Y
  • Journal Title: J Am Chem Soc. 129(48) Pages: 14840-1
• [Journal Article] Effect of N-terminal residues on the structural stability of recombinant horse L-chain apoferritin in an acidic environment. (2007)
  • Author(s): Yoshizawa K, Mishima Y, Park SY, Heddle JG, Tame JR, Iwahori K, Kobayashi M, Yamashita I.
  • Journal Title: J Biochem 142(6) Pages: 707-13
  • Peer Reviewed
• [Journal Article] Crystallization and preliminary crystallographic studies of the metallogl ycoprotein esterase A4 using a baculovirus expression system. (2007)
  • Author(s): Hiraki T, Shibayama N, Yoon YH, Yun KM, Hamamoto T, Tame JR, Park SY.
  • Journal Title: Acta Crystallogr Sect F Struct Biol Cryst Commun 63(Pt 9) Pages: 734-6
  • Peer Reviewed
• [Journal Article] Dynamic allostery in the ring protein TRAP. (2007)
  • Author(s): Heddle JG, Okajima T, Scott DJ, Akashi S, Park SY, Tame JR.
  • Journal Title: J Mol Biol. 371(1) Pages: 154-67
  • Peer Reviewed
• [Journal Article] Structure and mechanism of HpcG, a hydratase in the homoprotocatechuate degradation pathway of Escherichia coli. (2007)
  • Author(s): Izumi A, Rea D, Adachi T, Unzai S, Park SY, Roper DI, Tame JR.
  • Journal Title: J Mol Biol. 370(5) Pages: 899-911
  • Peer Reviewed
• [Presentation] Expression, purification and crystallization of LMW-PBP 4 and 5 from Haemophilus influenzae. (2008)
  • Author(s): Fumihiro Kawai, et al
  • Organizer: 第21回国際結晶学連合会議
  • Place of Presentation: 大阪
  • Year and Date: 2008-08-23
• [Presentation] Crystal structure of the clock protein EA4 from the silkworm bombyx mori (2008)
  • Author(s): Park SY, H. Hiraki, N. Shibayama, S. Akashi
  • Organizer: 2^<nd> International conference on protein science
  • Place of Presentation: Cairns Ausrralia
• [Presentation] Haemoglobin as a drug target (2008)
  • Author(s): Takeshi Yokoyama, Satoru Unzai, Park SY, Jeremy Tame
  • Organizer: The40th crystallographic meeting at Erice
  • Place of Presentation: Italy
• [Presentation] Crystal structures of the clock protein EA4 from the silkworm bombyx mori (2008)
  • Author(s): Park SY, T.Hiraki, N.Shibayama, S.Akashi
  • Organizer: The Joint 4th AOHUPO(Asian Oceania Human Proeome Organisation and 2nd PRICPS(Pacific Rim International Conference on Protein Science
  • Place of Presentation: Cairns, Australia
• [Presentation] Protonation states of buried histidine residues in human deoxyhemoglobin revealed by neutron crystallography (2008)
  • Author(s): Park SY, Toshiyuki Chatake, Naoya Shibayama, Yukiko Morimoto
  • Organizer: XVth International Conference on Oxygen Binding and Sensing Proteins
  • Place of Presentation: Aarhus, Denmark
• [Presentation] Studies of protein-protein and protein-RNA complexes by mass spectrometry, IUCr (2008)
  • Author(s): Satoko Akashi, Masahiro Watanabe, Jonathan GHeddle, Satoru Unzai, Park SY, Jeremy R.H.Tame
  • Organizer: 第21回国際結晶学連合会議
  • Place of Presentation: 大阪
• [Presentation] X-ray Crystallography of Autotransporters from Pathogenic Bacteria. (2007)
  • Author(s): Kaoru Nishimura, Sam-Yong Park, and Jeremy Tame
  • Organizer: Molecular Microbiology Young Microbiologists Minisymposium Prokaryotic Membranes.
  • Place of Presentation: Paris, France
  • Year and Date: 2007-10-12
• [Presentation] Dynamic allostery in the ring protein TRAP. Biophysics of ligand binding to drug targets. Workshop (2007)
  • Author(s): Heddle JG, Akashi S, Park SY, Tame JR
  • Organizer: llkirch, Strasbourg
  • Place of Presentation: France
• [Presentation] Crystal structure of penicillin binding protein 4 (dacB) from Escherichia coli (2007)
  • Author(s): Park SY, JRH Tame
  • Organizer: Biophysics of ligand binding to drug targets. Workshop, llkirch, Strasbourg
  • Place of Presentation: France
• [Presentation] Crystal structure of penicillin binding protein 4 (dacB) from Escherichia coli (2007)
  • Author(s): Park SY, JRH Tame
  • Organizer: 24^<th> European Crystallographic Meeting
  • Place of Presentation: Marrakech, Morocco
• [Presentation] Dynamic allostery in the tryptophan-binding protein TRAP (2007)
  • Author(s): Heddle JG, Akashi S, Park SY, Tame JR.
  • Organizer: Biophysics of ligand binding to drug tagets.
  • Place of Presentation: Strasbourg, France
• [Patent(Industrial Property Rights)] 抗生剤として有効な新規化合物 (2008)
  • Inventor(s): 朴 三用
  • Industrial Property Rights Holder: 横浜市立大学
  • Filing Date: 2008-08-22
• [Patent(Industrial Property Rights)] 新規抗生剤の開発
  • Inventor(s): 朴三用
  • Industrial Property Rights Holder: 横浜市立大学
  • Industrial Property Number: 2008-213424