1x80: Difference between revisions
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[[Image:1x80.gif|left|200px]]< | [[Image:1x80.gif|left|200px]] | ||
'''Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase''' | {{Structure | ||
|PDB= 1x80 |SIZE=350|CAPTION= <scene name='initialview01'>1x80</scene>, resolution 2.00Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=TDP:THIAMIN+DIPHOSPHATE'>TDP</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</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] | |||
|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]) | |||
}} | |||
'''Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1X80 is a [ | 1X80 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X80 OCA]. | ||
==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:// | 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: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: thiamin diphosphate]] | [[Category: thiamin diphosphate]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:06:12 2008'' | ||
Revision as of 16:06, 20 March 2008
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| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , and | ||||||
| Gene: | BCKDHA (Homo sapiens), BCKDHB (Homo sapiens) | ||||||
| Activity: | 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring), with EC number 1.2.4.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Maple syrup urine disease, type Ia OMIM:[608348], Maple syrup urine disease, type Ib OMIM:[248611]
About this StructureAbout this Structure
1X80 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- 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.
- CL
- GOL
- K
- MN
- TDP
- Acylation
- Branched-chain
- Flavoprotein
- Ketoacid dehydrogenase
- Multi-enzyme complex
- Oxidative decarboxylation maple syrup urine disease
- Oxidoreductase
- Phosphorylation
- Thiamin diphosphate