| Project/Area Number |
23510280
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Chemical biology
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| Research Institution | Toyama Prefectural University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
YAMADA Masato 富山県立大学, 工学部・生物工学科, 助教 (40448692)
HASHIMOTO Seiji 富山県立大学, 工学部・生物工学科, 教授 (20423832)
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | アシラーゼ / 抗生物質 / モデリング / 変異体 / 基質特異性 / 変異体酵素 / エキノキャンジン / ドッキング / 変異体設計 / ホモロジーモデリング / ドッキング計算 / 酵素 / ドッキングシミュレーション / 創薬 |
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| Outline of Final Research Achievements |
The antibiotic acylases are key enzymes for the industrial production of antibiotic drugs. Cephalosporin acylase (CA) is one of the most intensively studied enzymes that catalyze the deacylation of β-lactam antibiotics. On the other hand, aculeacin A acylase (AAC) is known to be an alternative acylase class catalyzing the deacylation of echinocandin compounds, but its structural and enzymatic properties remain to be explored.
In the present study, 3D homology models of AAC were constructed, and docking simulation with substrate ligands was performed for AAC. Based on the computation results, CA mutants have been designed to form the binding site for aculeacin A. Experimentally synthesized mutant enzymes exhibited lower enzymatic activity for cephalosporin but higher activity for aculeacin A, in comparison with the wild-type enzyme. The present results demonstrate the usefulness of the computational approaches for engineering the enzymatic properties of antibiotic acylases.
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