Structure and mechanism of the iron transport system in human

• Project/Area Number: 24687015
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Sugimoto Hiroshi 国立研究開発法人理化学研究所, 放射光科学総合研究センター, 専任研究員 (90344043)
• Research Collaborator: Hiromi Togashi ; Takeshi Urano ; Nami Yashima ; Hanae Takeda ; Mauk Grant A.
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥27,300,000 (Direct Cost: ¥21,000,000、Indirect Cost: ¥6,300,000); Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2013: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000); Fiscal Year 2012: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 金属タンパク質 / 鉄イオン / 金属イオン / ヘム / トランスポーター / X線 / 結晶

Outline of Final Research Achievements

We performed the structural and functional analysis of transmembrane ferrireductase expressed in human duodenal brush border membrane. This enzyme contains two hemes as a cofactor to mediate the electron transfer from intracellular ascorbic acid (Asc) to ferric iron in the intestinal lumen. Our stopped-flow kinetic analysis of the ferrireductase and its mutants in the detergent solution suggested that the conserved positively charged residues are involved in Asc-binding. We obtained the crystals by the lipidic cubic phase method and determined the structure of ferrireductase.

Research Products

• [Int'l Joint Research] University of British Columbia(カナダ)
• [Journal Article] Crystal Structure of Response Regulator ChrA in the Heme-Sensing Two-Component System of Corynebacterium diphtheriae (2015)
  • Author(s): A. Doi, H. Nakamura, Y. Shiro, H. Sugimoto
  • Journal Title: Acta Crysll. F Volume: 71 Issue: 8 Pages: 966-971
  • DOI: 10.1107/s2053230x15009838
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Structural basis for the transcriptional regulation of heme homeostasis in Lactococcus lactis (2012)
  • Author(s): H. Sawai
  • Journal Title: J. Biol. Chem. Volume: 287 Issue: 36 Pages: 30755-30768
  • DOI: 10.1074/jbc.m112.370916
  • Peer Reviewed
• [Journal Article] Structural Basis for Oxygen Sensing and Signal Transduction of the Heme-Based Sensor Protein Aer2 from Pseudomonas aeruginosa (2012)
  • Author(s): H. Sawai, H. Sugimoto, Y. Shiro, H. Ishikawa, Y. Mizutani, S. Aono
  • Journal Title: Chem. Commun Volume: 48 Issue: 52 Pages: 6523-6525
  • DOI: 10.1039/c2cc32549g
  • Peer Reviewed
• [Journal Article] Structural Basis for Nitrous Oxide Generation by Bacterial Nitric Oxide Reductases (2011)
  • Author(s): Y.Shiro, H.Sugimoto, T.Tosha, S.Nagano, T.Hino
  • Journal Title: Philosophical Transactions of the Royal Society B Volume: 00 Issue: 1593 Pages: 1-9
  • DOI: 10.1098/rstb.2011.0310
  • Peer Reviewed
• [Presentation] Stopped-flow kinetic analysis of human duodenal cytochrome b561 (2015)
  • Author(s): Hanae Takeda, Hiromi Togashi, Tetsunari Kimura, Grant Mauk, Hiroshi Sugimoto, Yoshitsugu Shiro
  • Organizer: International Chemical Congress of Pacific Basin Societies (PACIFICHEM 2015)
  • Place of Presentation: アメリカ, ホノルル, Hawaii Convention Center
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] ヒト由来Dcytbによる非ヘム鉄還元反応の速度論解析 (2015)
  • Author(s): 冨樫ひろ美、武田英恵、木村哲就、Grant A. Mauk、杉本宏、城宜嗣
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学会大会 合同年会
  • Place of Presentation: 兵庫県神戸市神戸国際会議場
  • Year and Date: 2015-12-01
• [Presentation] ヒト由来鉄還元酵素Dcytbの機能解析と結晶化 (2015)
  • Author(s): 冨樫ひろ美、武田英恵、木村哲就、Grant A. Mauk、杉本宏、城宜嗣
  • Organizer: 平成27年度日本結晶学会年会
  • Place of Presentation: 大阪府堺市大阪府立大学
  • Year and Date: 2015-10-17
• [Presentation] ヒト由来鉄還元酵素Dcytbの反応速度論解析 (2015)
  • Author(s): 武田英恵、冨樫ひろ美、木村哲就、Grant Mauk、杉本宏、城宜嗣
  • Organizer: 第9回バイオ関連科学シンポジウム
  • Place of Presentation: 熊本県熊本市熊本大学
  • Year and Date: 2015-09-10
• [Presentation] ヒト由来鉄還元酵素DcytbのStopped-Flow法による機能解析 (2015)
  • Author(s): 武田英恵、冨樫ひろ美、木村哲就、Grant Mauk、杉本宏、城宜嗣
  • Organizer: 第15回日本蛋白質科学会年会
  • Place of Presentation: 徳島県徳島市あわぎんホール
  • Year and Date: 2015-06-24
• [Presentation] ヒトの鉄吸収に関与する膜タンパク質Dcytbの結晶化と鉄還元反応に関する研究 (2015)
  • Author(s): 冨樫ひろ美, 武田英恵, 杉本 宏, G. Mauk, 城 宜嗣
  • Organizer: 第15回日本蛋白質科学会年会
  • Place of Presentation: 徳島県徳島市あわぎんホール
  • Year and Date: 2015-06-24
• [Presentation] Stopped-flow Analysis on the Reaction of Ascorbate with Duodenal Cytochrome b561 (2015)
  • Author(s): Hanae Takeda, Hiromi Togashi, Tetsunari Kimura, Grant A. Mauk, Hiroshi Sugimoto, Yoshitsugu Shiro
  • Organizer: Metals in Biology in Wako
  • Place of Presentation: 埼玉県和光市理化学研究所
  • Year and Date: 2015-06-16
  • Int'l Joint Research
• [Presentation] 鉄吸収に関与するヒト由来Cytochrome b561の電子伝達機構の解明 (2014)
  • Author(s): 冨樫 ひろ美, 杉本 宏, Grant Mauk, 城 宜嗣
  • Organizer: 第27回生物無機化学夏季セミナー
  • Place of Presentation: 兵庫県姫路市 円教寺会館
  • Year and Date: 2014-08-29 – 2014-08-31
• [Presentation] ヒト由来鉄還元タンパク質Dcytbの分子内電子移動反応に関する研究 (2014)
  • Author(s): 冨樫 ひろ美, 杉本 宏, Grant Mauk, 城 宜嗣
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: 神奈川県横浜市 ワークピア横浜
  • Year and Date: 2014-06-25 – 2014-06-27
• [Presentation] ヒトの鉄吸収に関わる膜タンパク質Dcytbの電子伝達機構の解明 (2014)
  • Author(s): 冨樫 ひろ美, 杉本 宏, Grant Mauk, 城 宜嗣
  • Organizer: 分子システム研究第3回春季研究会
  • Place of Presentation: 滋賀県彦根市 かんぽの宿彦根
  • Year and Date: 2014-04-24 – 2014-04-25
• [Presentation] Transmembrane Electron Transfere by Human Duodenal cytochrome b (2013)
  • Author(s): 冨樫ひろ美, 杉本 宏, Grant Mauk, 城 宜嗣
  • Organizer: 第86回生化学大会
  • Place of Presentation: 横浜、パシフィコ横浜
• [Presentation] Reaction mechanism of indoleamine 2,3-dioxygenase revealed by crystallo graphic and spectroscopic analysis (2012)
  • Author(s): Hiroshi Sugimoto
  • Organizer: 13th Symposium of the International Study Group of Tryptophan Research
  • Place of Presentation: Masonic Centre (Sydney, Australia)(招待講演)
  • Year and Date: 2012-11-08