Neutron Diffraction Analysis of Human Farnesyl Pyrophosphate Synthase in Complex with Bisphosphonate
Project/Area Number |
25860022
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Physical pharmacy
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Research Institution | University of Toyama |
Principal Investigator |
Yokoyama Takeshi 富山大学, 医学薬学研究部(薬学), 助教 (50524162)
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Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | 構造生物学 / 中性子結晶構造解析 / 医薬品化学 / 構造活性相関 / プロトン化状態 / pH / リン酸基 / ビスホスホネート / ファルネシル二リン酸合成酵素 / イソペンテニル二リン酸 / 蛋白質科学 / 生物物理学 / リセドロネート / 大型結晶化 / BIODIFF |
Outline of Final Research Achievements |
Neutron crystal structure of human farnesyl pyrophosphate synthase (FPPS) in complex with risedronate (RIS) was determined, and the protonation state and hydration of RIS were elucidated. The structural analysis revealed that the phosphate groups of RIS were fully deprotonated with the abnormally decreased pKa. In addition, it was suggested that the roles of E93 and D264 consisted of canceling the extra negative charges upon the binding of ligands. This information would be helpful for the development of non-bisphosphonate FPPS inhibitors.
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Structural stabilization of transthyretin by a new compound, 6-benzoyl-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione2015
Author(s)
Yokoyama T, Takaki S, Chosa K, Sato T, Suico MA, Teranishi Y, Shuto T, Mizuguchi M, Kai H
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Journal Title
J Pharmacol Sci.
Volume: 129
Issue: 4
Pages: 240-243
DOI
Related Report
Peer Reviewed / Open Access
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