1ivh
From Proteopedia
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STRUCTURE OF HUMAN ISOVALERYL-COA DEHYDROGENASE AT 2.6 ANGSTROMS RESOLUTION: STRUCTURAL BASIS FOR SUBSTRATE SPECIFICITY
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Overview
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.
Disease
Known disease associated with this structure: Isovaleric acidemia OMIM:[607036]
About this Structure
1IVH is a Single protein structure of sequence from Homo sapiens with FAD and COS as ligands. Active as Isovaleryl-CoA dehydrogenase, with EC number 1.3.99.10 Full crystallographic information is available from OCA.
Reference
Structure of human isovaleryl-CoA dehydrogenase at 2.6 A resolution: structural basis for substrate specificity,., Tiffany KA, Roberts DL, Wang M, Paschke R, Mohsen AW, Vockley J, Kim JJ, Biochemistry. 1997 Jul 15;36(28):8455-64. PMID:9214289
Page seeded by OCA on Mon Nov 12 17:35:07 2007
