1lc3
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Crystal Structure of a Biliverdin Reductase Enzyme-Cofactor Complex
OverviewOverview
Biliverdin reductase (BVR) catalyzes the last step in heme degradation by, reducing the gamma-methene bridge of the open tetrapyrrole, biliverdin, IXalpha, to bilirubin with the concomitant oxidation of a, beta-nicotinamide adenine dinucleotide (NADH) or beta-nicotinamide adenine, dinucleotide phosphate (NADPH) cofactor. Bilirubin is the major bile, pigment in mammals and has antioxidant and anticompliment activity. We, have determined X-ray crystal structures of apo rat BVR and its complex, with NADH at 1.2 A and 1.5 A resolution, respectively. In agreement with, an independent structure determination of the apo-enzyme, BVR consists of, an N-terminal dinucleotide-binding domain (Rossmann-fold) and a C-terminal, domain that contains a six-stranded beta-sheet that is flanked on one face, by several alpha-helices. The C-terminal and N-terminal domains interact, extensively, forming the active site cleft at their interface. The, cofactor complex structure reported here reveals that the cofactor, nicotinamide ring extends into the active site cleft, where it is adjacent, to conserved amino acid residues and, consistent with the known, stereochemistry of the reaction catalyzed by BVR, the si face of the ring, is accessible for hydride transfer. The only titratable side-chain that, appears to be suitably positioned to function as a general acid in, catalysis is Tyr97. This residue, however, is not essential for catalysis, since the Tyr97Phe mutant protein retains 50% activity. This finding, suggests that the dominant role in catalysis may be performed by hydride, transfer from the cofactor, a process that may be promoted by proximity of, the invariant residues Glu96, Glu123, and Glu126, to the nicotinamide, ring.
About this StructureAbout this Structure
1LC3 is a Single protein structure of sequence from Rattus norvegicus with PO4 and NAD as ligands. Active as Biliverdin reductase, with EC number 1.3.1.24 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of a biliverdin IXalpha reductase enzyme-cofactor complex., Whitby FG, Phillips JD, Hill CP, McCoubrey W, Maines MD, J Mol Biol. 2002 Jun 21;319(5):1199-210. PMID:12079357
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