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| {{STRUCTURE_1x80| PDB=1x80 | SCENE= }} | | {{STRUCTURE_1x80| PDB=1x80 | SCENE= }} |
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| '''Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase'''
| | ===Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase=== |
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| ==Overview==
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| The human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) is a 4 MDa macromolecular machine comprising three catalytic components (E1b, E2b, and E3), a kinase, and a phosphatase. The BCKDC overall activity is tightly regulated by phosphorylation in response to hormonal and dietary stimuli. We report that phosphorylation of Ser292-alpha in the E1b active site channel results in an order-to-disorder transition of the conserved phosphorylation loop carrying the phosphoryl serine. The conformational change is triggered by steric clashes of the phosphoryl group with invariant His291-alpha that serves as an indispensable anchor for the phosphorylation loop through bound thiamin diphosphate. Phosphorylation of Ser292-alpha does not severely impede the E1b-dependent decarboxylation of alpha-ketoacids. However, the disordered loop conformation prevents phosphorylated E1b from binding the E2b lipoyl-bearing domain, which effectively shuts off the E1b-catalyzed reductive acylation reaction and therefore completely inactivates BCKDC. This mechanism provides a paradigm for regulation of mitochondrial alpha-ketoacid dehydrogenase complexes by phosphorylation. | | The line below this paragraph, {{ABSTRACT_PUBMED_15576032}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15576032 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15576032}} |
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| ==Disease== | | ==Disease== |
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| [[Category: Phosphorylation]] | | [[Category: Phosphorylation]] |
| [[Category: Thiamin diphosphate]] | | [[Category: Thiamin diphosphate]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:41:14 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:53:45 2008'' |