1umd
From Proteopedia
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| - | [[Image:1umd.gif|left|200px]] | + | [[Image:1umd.gif|left|200px]] |
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| - | '''branched-chain 2-oxo acid dehydrogenase (E1) from Thermus thermophilus HB8 with 4-methyl-2-oxopentanoate as an intermediate''' | + | {{Structure |
| + | |PDB= 1umd |SIZE=350|CAPTION= <scene name='initialview01'>1umd</scene>, resolution 1.90Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TDP:THIAMIN+DIPHOSPHATE'>TDP</scene> and <scene name='pdbligand=COI:2-OXO-4-METHYLPENTANOIC ACID'>COI</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= | ||
| + | }} | ||
| + | |||
| + | '''branched-chain 2-oxo acid dehydrogenase (E1) from Thermus thermophilus HB8 with 4-methyl-2-oxopentanoate as an intermediate''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1UMD is a [ | + | 1UMD is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UMD OCA]. |
==Reference== | ==Reference== | ||
| - | Ligand-induced conformational changes and a reaction intermediate in branched-chain 2-oxo acid dehydrogenase (E1) from Thermus thermophilus HB8, as revealed by X-ray crystallography., Nakai T, Nakagawa N, Maoka N, Masui R, Kuramitsu S, Kamiya N, J Mol Biol. 2004 Apr 2;337(4):1011-33. PMID:[http:// | + | Ligand-induced conformational changes and a reaction intermediate in branched-chain 2-oxo acid dehydrogenase (E1) from Thermus thermophilus HB8, as revealed by X-ray crystallography., Nakai T, Nakagawa N, Maoka N, Masui R, Kuramitsu S, Kamiya N, J Mol Biol. 2004 Apr 2;337(4):1011-33. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15033367 15033367] |
[[Category: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)]] | [[Category: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: riken structural genomics/proteomics initiative]] | [[Category: riken structural genomics/proteomics initiative]] | ||
[[Category: rsgi]] | [[Category: rsgi]] | ||
| - | [[Category: structural | + | [[Category: structural genomic]] |
| - | ''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 14:33:54 2008'' |
Revision as of 12:33, 20 March 2008
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| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring), with EC number 1.2.4.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
branched-chain 2-oxo acid dehydrogenase (E1) from Thermus thermophilus HB8 with 4-methyl-2-oxopentanoate as an intermediate
Overview
The alpha(2)beta(2) tetrameric E1 component of the branched-chain 2-oxo acid (BCOA) dehydrogenase multienzyme complex is a thiamin diphosphate (ThDP)-dependent enzyme. E1 catalyzes the decarboxylation of a BCOA concomitant with the formation of the alpha-carbanion/enamine intermediate, 2-(1-hydroxyalkyl)-ThDP, followed by transfer of the 1-hydroxyalkyl group to the distal sulfur atom on the lipoamide of the E2 component. In order to elucidate the catalytic mechanism of E1, the alpha- and beta-subunits of E1 from Thermus thermophilus HB8 have been co-expressed in Escherichia coli, purified and crystallized as a stable complex, and the following crystal structures have been analyzed: the apoenzyme (E1(apo)), the holoenzyme (E1(holo)), E1(holo) in complex with the substrate analogue 4-methylpentanoate (MPA) as an ES complex model, and E1(holo) in complex with 4-methyl-2-oxopentanoate (MOPA) as the alpha-carbanion/enamine intermediate (E1(ceim)). Binding of cofactors to E1(apo) induces a disorder-order transition in two loops adjacent to the active site. Furthermore, upon binding of MPA to E1(holo), the loop comprised of Gly121beta-Gln131beta moves close to the active site and interacts with MPA. The carboxylate group of MPA is recognized mainly by Tyr86beta and N4' of ThDP. The hydrophobic moiety of MPA is recognized by Phe66alpha, Tyr95alpha, Met128alpha and His131alpha. As an intermediate, MOPA is decarboxylated and covalently linked to ThDP, and the conformation of the protein loop is almost the same as in the substrate-free (holoenzyme) form. These results suggest that E1 undergoes an open-closed conformational change upon formation of the ES complex with a BCOA, and the mobile region participates in the recognition of the carboxylate group of the BCOA. ES complex models of E1(holo).MOPA and of E1(ceim).lipoamide built from the above structures suggest that His273alpha and His129beta' are potential proton donors to the carbonyl group of a BCOA and to the proximal sulfur atom on the lipoamide, respectively.
About this Structure
1UMD is a Protein complex structure of sequences from Thermus thermophilus. Full crystallographic information is available from OCA.
Reference
Ligand-induced conformational changes and a reaction intermediate in branched-chain 2-oxo acid dehydrogenase (E1) from Thermus thermophilus HB8, as revealed by X-ray crystallography., Nakai T, Nakagawa N, Maoka N, Masui R, Kuramitsu S, Kamiya N, J Mol Biol. 2004 Apr 2;337(4):1011-33. PMID:15033367
Page seeded by OCA on Thu Mar 20 14:33:54 2008
Categories: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) | Protein complex | Thermus thermophilus | Kamiya, N. | Kuramitsu, S. | Maoka, N. | Masui, R. | Nakagawa, N. | Nakai, T. | RSGI, RIKEN Structural Genomics/Proteomics Initiative. | COI | MG | TDP | Alpha(2)beta(2) tetramer | Riken structural genomics/proteomics initiative | Rsgi | Structural genomic
