1IVH

STRUCTURE OF HUMAN ISOVALERYL-COA DEHYDROGENASE AT 2.6 ANGSTROMS RESOLUTION: STRUCTURAL BASIS FOR SUBSTRATE SPECIFICITY

1IVH の概要

• エントリーDOI: 10.2210/pdb1ivh/pdb
• 分子名称: ISOVALERYL-COA DEHYDROGENASE, FLAVIN-ADENINE DINUCLEOTIDE, COENZYME A PERSULFIDE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, acyl-coa dehydrogenase, flavoprotein, isovaleryl-coa, isovaleric acidemia
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion matrix: P26440
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 178822.50

構造登録者

Tiffany, K.A.,Roberts, D.L.,Wang, M.,Paschke, R.,Mohsen, A.-W.A.,Vockley, J.,Kim, J.J.P. (登録日: 1997-05-15, 公開日: 1998-05-20, 最終更新日: 2024-10-23)

主引用文献

Tiffany, K.A.,Roberts, D.L.,Wang, M.,Paschke, R.,Mohsen, A.W.,Vockley, J.,Kim, J.J.
Structure of human isovaleryl-CoA dehydrogenase at 2.6 A resolution: structural basis for substrate specificity,.
Biochemistry, 36:8455-8464, 1997

PubMed Abstract: Isovaleryl-CoA dehydrogenase (IVD) belongs to an important flavoprotein family of acyl-CoA dehydrogenases that catalyze the alpha,beta-dehydrogenation of their various thioester substrates. Although enzymes from this family share similar sequences, catalytic mechanisms, and structural properties, the position of the catalytic base in the primary sequence is not conserved. E376 has been confirmed to be the catalytic base in medium-chain (MCAD) and short-chain acyl-CoA dehydrogenases and is conserved in all members of the acyl-CoA dehydrogenase family except for IVD and long-chain acyl-CoA dehydrogenase. To understand this dichotomy and to gain a better understanding of the factors important in determining substrate specificity in this enzyme family, the three-dimensional structure of human IVD has been determined. Human IVD expressed in Escherichia coli crystallizes in the orthorhombic space group P212121 with unit cell parameters a = 94.0 A, b = 97.7 A, and c = 181.7 A. The structure of IVD was solved at 2.6 A resolution by the molecular replacement method and was refined to an R-factor of 20.7% with an Rfree of 28.8%. The overall polypeptide fold of IVD is similar to that of other members of this family for which structural data are available. The tightly bound ligand found in the active site of the structure of IVD is consistent with that of CoA persulfide. The identity of the catalytic base was confirmed to be E254, in agreement with previous molecular modeling and mutagenesis studies. The location of the catalytic residue together with a glycine at position 374, which is a tyrosine in all other members of the acyl-CoA dehydrogenase family, is important for conferring branched-chain substrate specificity to IVD.

PubMed: 9214289
DOI: 10.1021/bi970422u

実験手法

X-RAY DIFFRACTION (2.6 Å)