1he2

From Proteopedia

Revision as of 14:08, 18 December 2007

HUMAN BILIVERDIN IX BETA REDUCTASE: NADP/BILIVERDIN IX ALPHA TERNARY COMPLEX

Overview

Biliverdin IXbeta reductase (BVR-B) catalyzes the pyridine, nucleotide-dependent production of bilirubin-IXbeta, the major heme, catabolite during early fetal development. BVR-B displays a preference for, biliverdin isomers without propionates straddling the C10 position, in, contrast to biliverdin IXalpha reductase (BVR-A), the major form of BVR in, adult human liver. In addition to its tetrapyrrole clearance role in the, fetus, BVR-B has flavin and ferric reductase activities in the adult. We, have solved the structure of human BVR-B in complex with NADP+ at 1.15 A, resolution. Human BVR-B is a monomer displaying an alpha/beta dinucleotide, binding fold. The structures of ternary complexes with mesobiliverdin, IValpha, biliverdin IXalpha, FMN and lumichrome show that human BVR-B has, a single substrate binding site, to which substrates and inhibitors bind, primarily through hydrophobic interactions, explaining its broad, specificity. The reducible atom of both biliverdin and flavin substrates, lies above the reactive C4 of the cofactor, an appropriate position for, direct hydride transfer. BVR-B discriminates against the biliverdin, IXalpha isomer through steric hindrance at the bilatriene side chain, binding pockets. The structure also explains the enzyme's preference for, NADP(H) and its B-face stereospecificity.

About this Structure

1HE2 is a Single protein structure of sequence from Homo sapiens with NAP and BLA as ligands. Active as Biliverdin reductase, with EC number 1.3.1.24 Known structural/functional Sites: and . Full crystallographic information is available from OCA.

Reference

Structure of human biliverdin IXbeta reductase, an early fetal bilirubin IXbeta producing enzyme., Pereira PJ, Macedo-Ribeiro S, Parraga A, Perez-Luque R, Cunningham O, Darcy K, Mantle TJ, Coll M, Nat Struct Biol. 2001 Mar;8(3):215-20. PMID:11224564

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