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2010 Fiscal Year Final Research Report

A developmental approach to clarify a molecular mechanism of transporter utilizing a model transporter as a light-driven ion pump

Research Project

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Project/Area Number 20590031
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionMatsuyama University

Principal Investigator

MIYAUCHI Seiji  Matsuyama University, 薬学部, 教授 (30202352)

Co-Investigator(Kenkyū-buntansha) KIKUKAWA Takashi  北海道大学, 創成科学共同研究機構, 助教 (20281842)
Project Period (FY) 2008 – 2010
Keywords生物物理化学 / トランスポーター / 光駆動性イオンポンプ / ハロロドプシン / 輸送分子機構 / スイッチ機構 / 分子弁
Research Abstract

Halorhodopsin (HR) is a light-driven inward-directed Cl^- pump. To clarify the molecular mechanism of Cl^- transport in detail, we precisely determined the transport activities through HR with various physicochemical techniques, and the following results were obtained.
(1) The crystal structure clearly shows that the primary Cl^- is proximal to the protonated Schiff base (PSB) and is stabilized by electrostatic interactions with the positive charged PSB [PDB : 1E12]. Based on the crystal structure, we mutated amino acid residues, which might be involved in Cltransport. Several important amino acid residues were identified ; Arg123, Ser130 and Asp252.
(2) Especially, two amino acid residues Ser130 and Asp252 were proved out to play an important role in Cl^- translocation away from the binding site in the extracellular (EC) channel across the retinal.
(3) For the sake of the vectorial translocation, HR protein must possess one or several molecular valves in HR to hinder the Cl^- leakage, or backflow (from cytoplasmic (CP) to EC channel) during pumping cycles. Ser130 coordinates with PBS and functions as a molecular valve to hinder the internal leak, backflux of Cl^- during anion-transport cycle.

  • Research Products

    (18 results)

All 2010 2009 2008

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (9 results) Book (2 results)

  • [Journal Article] Sodium-coupled electrogenic transport of pyroglutamate (5-oxoproline) via SLC5A8, a monocarboxylate transporter.2010

    • Author(s)
      Miyauchi S., Gopal E., Babu E., Srinivas S.R., Kubo Y., Umapathy N. S., Thakkar S.V., Ganapathy V., Prasad P.D.
    • Journal Title

      Biochim Biophys Acta 1798

      Pages: 1164-1171

    • Peer Reviewed
  • [Journal Article] Kinetic study of anti-viral ribavirin uptake mediated by hCNT3 and hENT1 in Xenopus laevis oocytes.2010

    • Author(s)
      Yamamoto T., Sugawara M., Kikukawa T., Miyauchi, S., Yamaguchi M., Tero A., Takagi S., Nakagaki T.
    • Journal Title

      Biophysical Chemistry 147

      Pages: 59-65

    • Peer Reviewed
  • [Journal Article] Role of Arg123 in light-driven anion pump mechanisms of pharaonis halorhodopsin.2009

    • Author(s)
      Kubo M., Kikukawa T., Miyauchi S., Seki A., Kamiya M., Aizawa T., Kawano K., Kamo N., Demura M.
    • Journal Title

      Photochem Photobiol 85

      Pages: 547-555

    • Peer Reviewed
  • [Journal Article] A tin oxide transparent electrode provides the means for rapid time-resolved pH measurements : application to photoinduced proton transfer of bacteriorhodopsin and proteorhodopsin.2009

    • Author(s)
      Tamogami J., Kikukawa T., Miyauchi S., Muneyuki E., Kamo N.
    • Journal Title

      Photochem Photobiol 85

      Pages: 578-589

    • Peer Reviewed
  • [Journal Article] Uptake of 3,4-methylenedioxy- methamphetamine and its related compounds by a proton-coupled transport system in Caco-2 cells.2008

    • Author(s)
      Kuwayama K., Inoue H., Kanamori T., Tsujikawa K., Miyaguchi H., Iwata Y., Miyauchi S., Kamo N., Kishi T.
    • Journal Title

      Biochim Biophys Acta 1778(1)

      Pages: 42-50

    • Peer Reviewed
  • [Journal Article] Studies on effects of external electric fields on halobacteria with fluorescence intensity and fluorescence lifetime imaging microscopy.2008

    • Author(s)
      Nakabayashi T., Wang H.P. Tsujimoto K., Miyauchi S., Kamo N., Ohta N.
    • Journal Title

      Chemistry Letters 37(5)

      Pages: 522-523

    • Peer Reviewed
  • [Journal Article] Stimulation of Na^+/Cl^--coupled opioid peptide transport system in SK-N-SH cells by L-kyotorphin, an endogenous substrate for H+-coupled peptide transporter PEPT2.2008

    • Author(s)
      Thakkar S.V., Miyauchi S., Prasad P.D., Ganapathy V.
    • Journal Title

      Drug Metab Pharmacokinet 23

      Pages: 254-262

    • Peer Reviewed
  • [Presentation] 光駆動性クロライドポンプにおける基質認識機構の解明2010

    • Author(s)
      宮内正二,下野和実,菊川峰志,出村誠,加茂直樹
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      桃太郎アリーナ,岡山
    • Year and Date
      20100300
  • [Presentation] ハロロドプシンのCl-移動中における,シッフ塩基のpKaの変化2010

    • Author(s)
      宮内正二,関顕照,下野和実,菊川峰志,出村誠,加茂直樹
    • Organizer
      第48回日本生物物理学会年会
    • Place of Presentation
      東北大学川内北キャンパス,仙台
    • Year and Date
      2010-09-20
  • [Presentation] アザイド存在下における,光駆動性クロライドポンプのイオン輸送2010

    • Author(s)
      宮内正二,関顕照,下野和実,菊川峰志,出村誠,加茂直樹
    • Organizer
      第5回トランスポーター研究会
    • Place of Presentation
      東京医科大学病院,東京
    • Year and Date
      2010-07-10
  • [Presentation] ファラオニスハロロドプシンのCl^-輸送機構におけるAsp252の役割2009

    • Author(s)
      菊川峰志,宮内正二,一尾裕章,北川拓,出村誠,加茂直樹
    • Organizer
      第47回日本生物物理学会年会
    • Place of Presentation
      アスティ徳島,徳島
    • Year and Date
      2009-11-01
  • [Presentation] Role of the aspartic acid residue adjacent to the retinylidene Schiff base in the light-driven Cl- pump halorhodopsin.2009

    • Author(s)
      Kikukawa T., Miyauchi S., Kitagawa Ichio H., T., Kamiya M., Aizawa T., Kawano K., Demura M., Kamo N
    • Organizer
      15^<th> International Congress on Photobiology
    • Place of Presentation
      Dusseldorf, Germany
    • Year and Date
      2009-06-23
  • [Presentation] ハロロドプシンポンプ機能におけるシッフ塩基近傍酸性残基の役割2008

    • Author(s)
      菊川峰志,宮内正二,関顕照,北川拓,出村誠,Vadivel Ganapathy,加茂直樹
    • Organizer
      第46回日本生物物理学会年会
    • Place of Presentation
      福岡国際会議場,福岡
    • Year and Date
      2008-12-05
  • [Presentation] Transport of neurotoxic monocarboxylates via the Na^+-coupled monocarboxylate transporter SMCT1 (SLC5A8).2008

    • Author(s)
      Miyauchi S., Dabazaki Y., Gopal E., Ganapathy V.
    • Organizer
      American Association of Pharmaceutical Scientists (AAPS) Annual Meeting
    • Place of Presentation
      Georgia World Congress Center, Atlanta
    • Year and Date
      2008-11-17
  • [Presentation] 光駆動クロライドイオンポンプ,ハロロドプシンのアザイド存在下におけるイオン輸送機構に関する研究2008

    • Author(s)
      宮内正二,青山健太郎,菊川峰志,出村誠,Vadivel Ganapathy,加茂直樹
    • Organizer
      第30回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      札幌コンベンションセンター,札幌
    • Year and Date
      2008-08-01
  • [Presentation] Vadivel Ganapathy and Naoki Kamo. Mechanism of proton transport via azide-bound halorhodopsin from Natronomonas pharaonis.2008

    • Author(s)
      Seiji Miyauchi, Akiteru Seki , Takashi Kikukawa, Kentaro Aoyama, Makoto Demura
    • Organizer
      第3回トランスポーター研究会
    • Place of Presentation
      京都大学,京都
    • Year and Date
      2008-06-08
  • [Book] コンパス-生物薬剤学(第2章「生体膜の構造と薬物の生体膜透過機構」)2010

    • Author(s)
      岩城正宏,伊藤智夫編
    • Total Pages
      13-29
    • Publisher
      南江堂,東京
  • [Book] 製剤化のサイエンス-基礎とCMC(第1部製剤材料,2章「分散系」)2010

    • Author(s)
      永井恒司,園部尚編
    • Total Pages
      24-52
    • Publisher
      じほう,東京

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Published: 2012-01-26   Modified: 2016-04-21  

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