1RX0

Crystal structure of isobutyryl-CoA dehydrogenase complexed with substrate/ligand.

1RX0 の概要

• エントリーDOI: 10.2210/pdb1rx0/pdb
• 分子名称: Acyl-CoA dehydrogenase family member 8, mitochondrial, 1,2-ETHANEDIOL, FLAVIN-ADENINE DINUCLEOTIDE, ... (6 entities in total)
• 機能のキーワード: flavoprotein, dehydrogenase, coenzyme a, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion : Q9UKU7
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 176903.89

構造登録者

Battaile, K.P.,Nguyen, T.V.,Vockley, J.,Kim, J.J. (登録日: 2003-12-18, 公開日: 2004-04-20, 最終更新日: 2024-02-14)

主引用文献

Battaile, K.P.,Nguyen, T.V.,Vockley, J.,Kim, J.J.
Structures of Isobutyryl-CoA Dehydrogenase and Enzyme-Product Complex: COMPARISON WITH ISOVALERYL- AND SHORT-CHAIN ACYL-COA DEHYDROGENASES.
J.Biol.Chem., 279:16526-16534, 2004

PubMed Abstract: The acyl-CoA dehydrogenases are a family of mitochondrial flavoproteins involved in the catabolism of fatty and amino acids. Isobutyryl-CoA dehydrogenase (IBD) is involved in the catabolism of valine and catalyzes the conversion of isobutyryl-CoA to methacrylyl-CoA. The crystal structure of IBD with and without substrate has been determined to 1.76-A resolution. The asymmetric unit contains a homotetramer with substrate/product bound in two monomers. The overall structure of IBD is similar to those of previously determined acyl-CoA dehydrogenases and consists of an NH2-terminal alpha-helical domain, a medial beta-strand domain and a C-terminal alpha-helical domain. The enzyme-bound ligand has been modeled in as the reaction product, methacrylyl-CoA. The location of Glu-376 with respect to the C-2-C-3 of the bound product and FAD confirms Glu-376 to be the catalytic base. IBD has a shorter and wider substrate-binding cavity relative to short-chain acyl-CoA dehydrogenase, permitting the optimal binding of the isobutyryl-CoA substrate. The dramatic lateral expansion of the binding cavity seen in isovaleryl-CoA dehydrogenase is not observed in IBD. The conserved tyrosine or phenylalanine that defines a side of the binding cavity in other acyl-CoA dehydrogenases is replaced by a leucine (Leu-375) in the current structure. Substrate binding changes the position of some residues lining the binding pocket as well as the position of the loop containing the catalytic glutamate and subsequent helix. Three clinical mutations have been modeled to the structure. The mutations do not affect substrate binding but instead appear to disrupt protein folding and/or stability.

PubMed: 14752098
DOI: 10.1074/jbc.M400034200

実験手法

X-RAY DIFFRACTION (1.77 Å)