Structural study on 3α-hydroxysteroid dehydrogenases
| Project/Area Number |
19790035
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Physical pharmacy
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
NAKAMURA Shota Osaka University, 微生物病研究所, 特任助教 (90432434)
|
|---|
| Project Period (FY) |
2007 – 2009
|
| Project Status |
Completed (Fiscal Year 2009)
|
| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥570,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| Keywords | 生物分子構造学 / 酵素 / 蛋白質 / 分子動力学 / X線結晶構造解析 / 補酵素 / 反応機構 / ステロイド / 酸化還元反応 |
|---|
| Research Abstract |
In this study, we performed a 100-ns molecular dynamics simulation of the 3α-hydroxysteroid dehydrogenase from Pseudomonas sp. B-0831 (Ps3αHSD) to elucidate the flexibility and mobility of the substrate-binding loop. During the simulation, the structure of the holo-subunit was kept unchanged because of NADH interaction with the substrate-binding loop. On the other hand, the substrate-binding loop in the apo-subunit opened and fluctuated largely. By careful observation of the simulation, we designed the next mutagenesis study and found that T188A mutant lost the ability of loop-helix transition and negative cooperativity for NADH binding. These results suggest that high mobility of the substrate-binding loop could produce Ps3αHSD with characteristic activities such as negative cooperativity for NADH binding.
|
Report
(4 results)
Research Products
(4 results)
