Study on the structure-function relationship of lipoyltransferase
| Project/Area Number |
14570109
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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 |
General medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
FUJIWARA Kazuko the University of Tokushima, the Institute for Enzyme Research, Associate Professor, 分子酵素学研究センター, 助教授 (20108880)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | lipote-protein ligase A / lipoyltransferase / lipoic acid / ATP / X-ray crystal structure / SAD / グリシン開裂酵素系 / α-ケト酸デヒドロゲナーゼ複合体 / Hタンパク質 |
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| Research Abstract |
Lipoate-protein ligase A (LplA) catalyzes the formation of lipoyl-AMP from lipoate and ATP and then transfers the lipoyl moiety to a specific lysine residue on acyltransferase subunit of x-ketoacid dehydrogenase complexes and on H-protein of the glycine cleavage system. The lypoyllysine arm plays a pivotal roll in the complexes by shuttling the reaction intermediate and reducing equivalents between the active site of the components of the complexes. We have determined the x-ray crystal structures of LplA from Escherichia coli complexed with ATP or lipoic acid and without substrate. The structure of LplA consists of a large N-terminal domain and a small C-terminal domain. The structure identifies the substrate-binding pocket at the interface between two domains. Carboxyl oxygen of lipoic acid interacts with histidine residue through hydrogen bonding in a hydrophobic pocket in the N-terminal domain. While, ATP is anchored to the peptide backbones in both the N-terminal and C-terminal domains through hydrogen bonding in the pocket close to lipoic acid. A distance between ct-P atom of ATP and carbonyl oxygen atom of lipoic acid is close enough to permit lipoic acid to initiate the nucleophile attack onto α-P atom of ATP. The structure explain the reason why the mammalian lipoyltransferase has no ability to activate lipoic acid.
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Report
(3 results)
Research Products
(9 results)
