2003 Fiscal Year Final Research Report Summary
Mechanism of Coupling ATP hydrolysis to Ca^<2+> transport in sarcoplasmic reticulum Ca^<2+>-ATPase
| Project/Area Number |
14580619
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
DAIHO Takashi Asahikawa Medical College, Biochemistry, Assistant professor, 医学部, 助教授 (90207267)
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| Project Period (FY) |
2002 – 2003
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| Keywords | sarcoplasmic reticulum / Ca^<2+>-ATPase / phosphorylated intermediate / Daner's disease / Active transport / SERCA / calcium pump / P-type ATPase |
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| Research Abstract |
1.Mg/F/E(Enzyme) complex of sarcoplasmic reticulum Ca^<2+>-ATPase is an stable analog of phosphorylated intermediate(EP). We have found that the solubilized and delipidated Mg/F/E is remarkably stable against denaturation. 2.The Ca^<2+>-ATPase has 3 cytoplasmic domains (A,P,N). We have found that interaction between Val^<200> loop of A domain and P domain is important for Ca^<2+>-translocation from EP.3.Glu40-Ser48 loop connect A domain and the 1st transmembrane segment. We have found that the adequate length of this loop is important for conformational transition of EP, which is critical for Ca^<2+> translocation. We found that some mutations in this loop region reported in the Darier's disease pedigrees will also cause inhibition of EP transition. 4.We have found that Arg^<334> is important for EP transition and Tyr^<122> for Ca^<2+> translocation after the transition of EP. We have proposed a model for coupling, in which energy of ATP hydrolysis is transmitted to Ca^<2+> transport site through the large movements of cytoplasmic domains. 5.We have shown that the complexes Be/F/E,Al/F/E, and Mg/F/E are stable analogs for the ground state, transition state, and enzyme/product in EP hydrolysis. We also found that the structural changes in the catalytic site in EP hydrolysis will close the lumenal gate for Ca^<2+> translocation to prevent Ca^<2+> leak form the lumen.
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Research Products
(15 results)
