1HE4

Human biliverdin IX beta reductase: NADP/FMN ternary complex

Summary for 1HE4

• Entry DOI: 10.2210/pdb1he4/pdb
• Related: 1HDO 1HE2 1HE3 1HE5
• Descriptor: BILIVERDIN IX BETA REDUCTASE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, FLAVIN MONONUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: biliverdin-ix beta reductase, foetal metabolism, haem degradation, flavin reductase, diaphorase, green haem binding protein, methaemoglobin reductase, alpha/beta dinucleotide binding fold
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 23348.10

Authors

Pereira, P.J.B.,Macedo-Ribeiro, S.,Parraga, A.,Perez-Luque, R.,Cunningham, O.,Darcy, K.,Mantle, T.J.,Coll, M. (deposition date: 2000-11-19, release date: 2001-02-28, Last modification date: 2023-12-13)

Primary citation

Pereira, P.J.B.,Macedo-Ribeiro, S.,Parraga, A.,Perez-Luque, R.,Cunningham, O.,Darcy, K.,Mantle, T.J.,Coll, M.
Structure of Human Biliverdin Ix Beta Reductase, an Early Fetal Bilirubin Ix Producing Enzyme
Nat.Struct.Biol., 8:215-, 2001

PubMed Abstract: 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.

PubMed: 11224564
DOI: 10.1038/84948

Experimental method

X-RAY DIFFRACTION (1.4 Å)