| Project/Area Number |
21390314
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Meiji Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TOGAWA Tadayasu 明治薬科大学, 薬学部, 教授 (80260983)
TSUKIMURA Takahiro 明治薬科大学, 薬学部, 助教 (50632783)
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| Co-Investigator(Renkei-kenkyūsha) |
TOGAWA Tadayasu 明治薬科大学, 薬学部, 教授 (80260983)
TSUKIMURA Takahiro 明治薬科大学, 薬学部, 助教 (50632783)
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| Project Period (FY) |
2009 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2010: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | リソソーム病 / ファブリー病 / ポンペ病 / α‐ガラクトシダーゼ A / 酸性α-グル コシダーゼ / α-ガラクトシダーゼ / α-グルコシダーゼ / リソソーム酵素 / 基質類似体 / 酵素増強療法 / 分子間相互作用 |
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| Research Abstract |
To obtain basic information useful for development of chaperone therapy for Fabry disease and Pompe disease, we examined the molecular interactions between α-galactosidase A /acid α-glucosidase and their substrate analogues by means of isothermal titration calorimetry and surface plasmon resonance biosensor assays, and first determined the thermodynamic and binding-kinetics parameters. Furthermore, the structural analysis in silico revealed that the chemicals fit into the active site pocket of the enzyme molecule and undergo hydrogen bonding with residues comprising the pocket. The side chain of the chemicals is thought to be oriented towards the entrance of the pocket. On the basis of the results, we designed a new chemical that strongly stabilizes a mutant enzyme. Thermodynamic and structural studies should provide us with a lot of information for improving chaperone therapy for Fabry disease and Pompe disease.
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