Elucidation of the molecular mechanism of ABC transporters
Project/Area Number |
24689029
|
Research Category |
Grant-in-Aid for Young Scientists (A)
|
Allocation Type | Partial Multi-year Fund |
Research Field |
Applied pharmacology
|
Research Institution | Kyoto University |
Principal Investigator |
KODAN Atsushi 京都大学, 物質ー細胞統合システム拠点, 助教 (80360543)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2012: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
|
Keywords | 生体分子 / 膜タンパク質 / 癌 / 多剤耐性 / 立体構造解析 / X線結晶構造解析 / ABCタンパク質 / P糖タンパク質 / 蛋白質 / 薬学 |
Outline of Final Research Achievements |
In this study, the highest-resolution crystal structures of a eukaryotic P-glycoprotein homolog from the red algae Cyanidioschyzon merolae, were determined in two forms: unbound at 2.6-angstrom resolution and bound to a unique allosteric inhibitor at 2.4-angstrom resolution. These structures, along with site-directed mutagenesis and transporter activity measurements, reveal the detailed architecture of the transporter, including a gate that opens to extracellular side and two gates that open to intramembranous region and the cytosolic side.
|
Report
(4 results)
Research Products
(9 results)
-
[Journal Article] Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog2014
Author(s)
Atsushi Kodan, Tomohiro Yamaguchi, Toru Nakatsu, Keita Sakiyama, Christopher Hipolito, Akane Fujioka, Ryo Hirokane, Keiji Ikeguchi, Bunta Watanabe, Jun Hiratake, Yasuhisa Kimura, Hiroaki Suga, Kazumitsu Ueda, Hiroaki Kato
-
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Volume: 111
Issue: 11
Pages: 4049-4054
DOI
Related Report
Peer Reviewed
-
-
[Presentation] High-resolution crystal structure of an ABC multidrug exporter from Cyanidioschyzon merolae, a thermophilic unicellular eukaryote.2014
Author(s)
Atsushi Kodan, Tomohiro Yamaguchi, Toru Nakatsu, Keita Sakiyama, Christopher J. Hipolito, Akane Fujioka, Ryo Hirokane, Yasuhisa Kimura, Hiroaki Suga, Kazumitsu Ueda, Hiroaki Kato
Organizer
ABC2014, the 5th FEBS Special Meeting “ ATP-Binding Cassette Proteins: From Multidrug Resistance to Genetic Disease”
Place of Presentation
Innsbruck, Austria
Related Report
-
[Presentation] Structure-based functional aspects of the ABC multidrug transporter, CmABCB1 from a thermophilic eukaryote.2014
Author(s)
Tomohiro Yamaguchi, Atsushi Kodan, Toru Nakatsu, Keita Sakiyama, Christopher J. Hipolito, Akane Fujioka, Ryo Hirokane, Yasuhisa Kimura, Hiroaki Suga, Kazumitsu Ueda, Hiroaki Kato
Organizer
ABC2014, the 5th FEBS Special Meeting “ ATP-Binding Cassette Proteins: From Multidrug Resistance to Genetic Disease”
Place of Presentation
Innsbruck, Austria
Related Report
-
-
-
-
-