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1x7w
From Proteopedia
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|PDB= 1x7w |SIZE=350|CAPTION= <scene name='initialview01'>1x7w</scene>, resolution 1.73Å | |PDB= 1x7w |SIZE=350|CAPTION= <scene name='initialview01'>1x7w</scene>, resolution 1.73Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TDP:THIAMIN+DIPHOSPHATE'>TDP</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= BCKDHA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), BCKDHB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= BCKDHA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), BCKDHB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1u5b|1u5b]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1x7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x7w OCA], [http://www.ebi.ac.uk/pdbsum/1x7w PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1x7w RCSB]</span> | ||
}} | }} | ||
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==Disease== | ==Disease== | ||
| - | Known | + | Known disease associated with this structure: Maple syrup urine disease, type Ia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608348 608348]], Maple syrup urine disease, type Ib OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=248611 248611]] |
==About this Structure== | ==About this Structure== | ||
| Line 33: | Line 36: | ||
[[Category: Tomchick, D R.]] | [[Category: Tomchick, D R.]] | ||
[[Category: Wynn, R M.]] | [[Category: Wynn, R M.]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: K]] | ||
| - | [[Category: MN]] | ||
| - | [[Category: TDP]] | ||
[[Category: acylation]] | [[Category: acylation]] | ||
[[Category: branched-chain]] | [[Category: branched-chain]] | ||
[[Category: flavoprotein]] | [[Category: flavoprotein]] | ||
| - | [[Category: ketoacid dehydrogenase]] | ||
[[Category: multi-enzyme complex]] | [[Category: multi-enzyme complex]] | ||
[[Category: oxidative decarboxylation maple syrup urine disease]] | [[Category: oxidative decarboxylation maple syrup urine disease]] | ||
| - | [[Category: oxidoreductase]] | + | [[Category: oxidoreductase,ketoacid dehydrogenase]] |
[[Category: phosphorylation]] | [[Category: phosphorylation]] | ||
[[Category: thiamin diphosphate]] | [[Category: thiamin diphosphate]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:45:54 2008'' |
Revision as of 21:45, 30 March 2008
| |||||||
| , resolution 1.73Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Gene: | BCKDHA (Homo sapiens), BCKDHB (Homo sapiens) | ||||||
| Activity: | 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring), with EC number 1.2.4.4 | ||||||
| Related: | 1u5b
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
1X7W 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 Mon Mar 31 00:45:54 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. | Acylation | Branched-chain | Flavoprotein | Multi-enzyme complex | Oxidative decarboxylation maple syrup urine disease | Oxidoreductase,ketoacid dehydrogenase | Phosphorylation | Thiamin diphosphate
