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Título

Structure of human biliverdin IXβ reductase, an early fetal bilirubin IXβ producing enzyme

Autor Pereira, Pedro José Barbosa; Macedo-Ribeiro, Sandra; Párraga, Antonio; Pérez-Luque, Rosa ; Cunningham, Orla; Darcy, Kevin J.; Mantle, Timothy J.; Coll, Miquel
Palabras clave lumichrome
flavoprotein
flavine mononucleotide
bilirubin
monomer
oxidoreductase
reduced nicotinamide adenine dinucleotide phosphate
biliverdin
Fecha de publicación 2001
EditorNature Publishing Group
Citación Nature Structural Biology 8(3): 215-220 (2001)
ResumenBiliverdin IXβ reductase (BVR-B) catalyzes the pyridine nucleotide-dependent production of bilirubin-IXβ, the major home catabolite during early fetal development. BVR-B displays a preference for biliverdin isomers without propionates straddling the C10 position, in contrast to biliverdin IXα 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 Å resolution. Human BVR-B is a monomer displaying an α/β dinucleotide binding fold. The structures of ternary complexes with mesobiliverdin IVα, biliverdin IXα, 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 CA of the cofactor, an appropriate position for direct hydride transfer. BVR-B discriminates against the biliverdin IXα 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.
Versión del editorhttp://dx.doi.org/10.1038/84948
URI http://hdl.handle.net/10261/108790
DOI10.1038/84948
Identificadoresdoi: 10.1038/84948
issn: 1072-8368
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