1HE2

Human biliverdin IX beta reductase: NADP/biliverdin IX alpha ternary complex

1HE2 の概要

• エントリーDOI: 10.2210/pdb1he2/pdb
• 関連するPDBエントリー: 1HDO 1HE3 1HE4 1HE5
• 分子名称: Flavin reductase (NADPH), NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, BILIVERDINE IX ALPHA, ... (4 entities in total)
• 機能のキーワード: biliverdin-ix beta reductase, foetal metabolism, haem degradation, flavin reductase, diaphorase, green haem binding protein, methaemoglobin reductase, alpha/beta dinucleotide binding fold
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23474.40

構造登録者

Pereira, P.J.B.,Macedo-Ribeiro, S.,Parraga, A.,Perez-Luque, R.,Cunningham, O.,Darcy, K.,Mantle, T.J.,Coll, M. (登録日: 2000-11-18, 公開日: 2001-02-28, 最終更新日: 2025-03-05)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.2 Å)