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1u5b
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(New page: 200px<br /> <applet load="1u5b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u5b, resolution 1.83Å" /> '''Crystal structure o...) |
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caption="1u5b, resolution 1.83Å" /> | caption="1u5b, resolution 1.83Å" /> | ||
'''Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase'''<br /> | '''Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1U5B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with K, MN, TDP and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-methyl-2-oxobutanoate_dehydrogenase_(2-methylpropanoyl-transferring) 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.4 1.2.4.4] Full crystallographic information is available from [http:// | + | 1U5B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=K:'>K</scene>, <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=TDP:'>TDP</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-methyl-2-oxobutanoate_dehydrogenase_(2-methylpropanoyl-transferring) 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.4 1.2.4.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U5B OCA]. |
==Reference== | ==Reference== | ||
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[[Category: thiamin diphosphate]] | [[Category: thiamin diphosphate]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:59:20 2008'' |
Revision as of 14:59, 15 February 2008
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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 diseases 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 with , , and as ligands. Active as 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring), with EC number 1.2.4.4 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 Fri Feb 15 16:59:20 2008
Categories: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) | Homo sapiens | Protein complex | Chuang, D.T. | Chuang, J.L. | Kato, M. | Li, J. | Machius, M. | Tomchick, D.R. | Wynn, R.M. | GOL | K | MN | TDP | Acylation | Branched-chain | Flavoprotein | Ketoacid dehydrogenase | Multi-enzyme complex | Oxidative decarboxylation maple syrup urine disease | Oxidoreductase | Phosphorylation | Thiamin diphosphate
