3mdd
From Proteopedia
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CRYSTAL STRUCTURES OF MEDIUM CHAIN ACYL-COA DEHYDROGENASE FROM PIG LIVER MITOCHONDRIA WITH AND WITHOUT SUBSTRATE
Overview
The three-dimensional structure of medium-chain acyl-CoA dehydrogenase, from pig mitochondria in the native form and that of a complex of the, enzyme and a substrate (product) have been solved and refined by x-ray, crystallographic methods at 2.4-A resolution to R factors of 0.172 and, 0.173, respectively. The overall polypeptide folding and the quaternary, structure of the tetramer are essentially unchanged upon binding of the, ligand, octanoyl (octenoyl)-CoA. The ligand binds to the enzyme at the, rectus (re) face of the FAD in the crevice between the two alpha-helix, domains and the beta-sheet domain of the enzyme. The fatty acyl chain of, the thioester substrate is buried inside of the polypeptide and the 3'-AMP, moiety is close to the surface of the tetrameric enzyme molecule. The, alkyl chain displaces the tightly bound water molecules found in the, native enzyme and the carbonyl oxygen of the thioester interacts with the, ribityl 2'-hydroxyl group of the FAD and the main-chain carbonyl oxygen of, Glu-376. The C alpha--C beta of the fatty acyl moiety lies between the, flavin and the gamma-carboxylate of Glu-376, supporting the role of, Glu-376 as the base that abstracts the alpha proton in the alpha--beta, dehydrogenation reaction catalyzed by the enzyme. Trp-166 and Met-165 are, located at the sinister (si) side of the flavin ring at the surface of the, enzyme, suggesting that they might be involved in the interactions with, electron transferring flavoprotein. Lys-304, the prevalent mutation site, found in patients with medium-chain acyl-CoA dehydrogenase deficiency, is, located approximately 20 A away from the active site of the enzyme.
About this Structure
3MDD is a Single protein structure of sequence from Sus scrofa with FAD as ligand. Active as Acyl-CoA dehydrogenase, with EC number 1.3.99.3 Full crystallographic information is available from OCA.
Reference
Crystal structures of medium-chain acyl-CoA dehydrogenase from pig liver mitochondria with and without substrate., Kim JJ, Wang M, Paschke R, Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7523-7. PMID:8356049
Page seeded by OCA on Tue Nov 20 19:51:43 2007
