2009 Fiscal Year Final Research Report
Structural study on 3α-hydroxysteroid dehydrogenases
| Project/Area Number |
19790035
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
NAKAMURA Shota Osaka University, 微生物病研究所, 特任助教 (90432434)
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| Project Period (FY) |
2007 – 2009
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| Keywords | 生物分子構造学 |
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| 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.
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