2013 Fiscal Year Final Research Report
Structural basis for optimization of molecular probe using P-glycoprotein in vivo imaging
| Project/Area Number |
24659018
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
KATO Hiroaki 京都大学, 薬学研究科(研究院), 教授 (90204487)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 分子イメージング / ABCトランスポーター / X線結晶解析 / P糖タンパク質 / 抗がん剤 |
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| Research Abstract |
In order to develop specific molecular probes for in vivo imaging of P-glycoprotein, an X-ray crystallographic analysis of a P-glycoprotein homolog in complex with some candidate molecules for the probe was performed and the structural basis of their interactions was elucidated. From the X-ray diffraction analysis clear electron density of the P-glycoprotein homolog was observed whereas the unclear density of the probe molecules was detected. A photometric assay of the complex crystals indicated that the probes were included in the crystals. These findings indicated that the probe candidates are weakly bound in the inner cavity of the P-glycoprotein homolog and their conformations are unfixed even in the crystalline state.
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[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
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Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Volume: 111
Pages: 4049-4054
DOI
Peer Reviewed
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