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1u5b
From Proteopedia
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[[Image:1u5b.jpg|left|200px]] | [[Image:1u5b.jpg|left|200px]] | ||
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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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==Reference== | ==Reference== | ||
Molecular mechanism for regulation of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex by phosphorylation., Wynn RM, Kato M, Machius M, Chuang JL, Li J, Tomchick DR, Chuang DT, Structure. 2004 Dec;12(12):2185-96. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15576032 15576032] | Molecular mechanism for regulation of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex by phosphorylation., Wynn RM, Kato M, Machius M, Chuang JL, Li J, Tomchick DR, Chuang DT, Structure. 2004 Dec;12(12):2185-96. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15576032 15576032] | ||
| - | [[Category: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: Tomchick, D R.]] | [[Category: Tomchick, D R.]] | ||
[[Category: Wynn, R M.]] | [[Category: Wynn, R M.]] | ||
| - | [[Category: | + | [[Category: Acylation]] |
| - | [[Category: | + | [[Category: Branched-chain]] |
| - | [[Category: | + | [[Category: Flavoprotein]] |
| - | [[Category: | + | [[Category: Multi-enzyme complex]] |
| - | [[Category: | + | [[Category: Oxidative decarboxylation maple syrup urine disease]] |
| - | [[Category: | + | [[Category: Oxidoreductase,ketoacid dehydrogenase]] |
| - | [[Category: | + | [[Category: Phosphorylation]] |
| - | [[Category: | + | [[Category: Thiamin diphosphate]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:46:22 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 07:46, 3 May 2008
Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase
Contents |
Overview
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.
Disease
Known disease associated with this structure: Maple syrup urine disease, type Ia OMIM:[608348], Maple syrup urine disease, type Ib OMIM:[248611]
About this Structure
1U5B is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Molecular mechanism for regulation of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex by phosphorylation., Wynn RM, Kato M, Machius M, Chuang JL, Li J, Tomchick DR, Chuang DT, Structure. 2004 Dec;12(12):2185-96. PMID:15576032 Page seeded by OCA on Sat May 3 10:46:22 2008
Categories: Homo sapiens | Protein complex | Chuang, D T. | Chuang, J L. | Kato, M. | Li, J. | Machius, M. | Tomchick, D R. | Wynn, R M. | Acylation | Branched-chain | Flavoprotein | Multi-enzyme complex | Oxidative decarboxylation maple syrup urine disease | Oxidoreductase,ketoacid dehydrogenase | Phosphorylation | Thiamin diphosphate
