Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Outline of Final Research Achievements |
The human pyruvate dehydrogenase kinase (PDHK) specifically regulates the reaction of pyruvate dehydrogenase complex (PDC). The function of PDHK is allosterically inhibited by ADP and pyruvate. In this study, to understand the regulation of PDHK, the dynamical structural changes of the C-terminal cross arm structure by binding ligands and chemical modification was analyzed using fluorescence of Trp383 in PDHK2. The binding of ADP and pyruvate induced substantial dynamical changes of C-terminal cross arm structure of PDHK2 as well as PDHK1. Chemical modification of Cys384 by NEM introduced similar effects on the cross arm structure. Analytical ultracentrifuge analysis using NEM-PDHK2 suggests that the dislocation of cross arm structure led to dissociate PDHK2 from inner lioyl domain of E2, which could cause the significant loss of the accessibility to substrate E1.
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