Biliverdin reductase B is a protein that in humans is encoded by the BLVRB gene.[5]
BLVRB | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | BLVRB, BVRB, FLR, HEL-S-10, SDR43U1, Biliverdin reductase B | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 600941; MGI: 2385271; HomoloGene: 573; GeneCards: BLVRB; OMA:BLVRB - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
EC number | 1.3.1.24 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure
editThe BLVRB gene was localized to chromosome 19, the specific region being 19q13.13 to q13.2; this was done using fluorescence in situ hybridization.[6]
BLVRB encodes a protein that is a 206-residue monomeric enzyme.[7] The structure of BVR-B has a single-domain architecture consisting of a central parallel beta-sheet with alpha-helices on either side. This characteristic dinucleotide binding fold comprises, in this case, a seven-stranded parallel beta-sheet further extended by an antiparallel strand. In addition to the seven long strands of the main pleated sheet, a short parallel beta-sheet (strands 6a and 6c) is formed within the loop joining strand 6 and alpha-helix F. The central beta-sheet and the two groups of helices are held together mainly through hydrophobic interactions. One group of helices is made up of alpha-helices C, D, and E. The second group is composed of alpha-helices A and F and includes a short 310-helix between strands beta2 and beta3, in contrast to typical dinucleotide binding proteins in which a regular alpha-helix flanks these beta-strands. The most flexible loop in the structure corresponds to loop 120, between strand 5 and alpha-helix E, which contains residues with the highest main chain B-factors, with the exception of the N-terminal region.[8]
Function
editThe final step in heme metabolism in mammals is catalyzed by the cytosolic biliverdin reductase enzymes A and B (EC 1.3.1.24).[5] From a functional standpoint, it has been hypothesized that BLRVB is identical to flavin reductase (FR), an enzyme that catalyzes the NADPH-dependent reduction of FMN and Methylene Blue and, in the presence of redox couplers, the reduction of methaemoglobin.[9][10]
There have been two isoforms of BLVRB, I and II, that have been isolated and characterized. The purified enzymes were monomers with a molecular weight of about 21,000, and they used NADPH and NADH as electron donors for the reduction of biliverdin. The identified Km values of isozymes I and II for NADPH are 35.9 and 13.1
Clinical significance
editAs BLVRB is a promiscuous enzyme catalysing the pyridine-nucleotide-dependent reduction of a variety of flavins, biliverdins, PQQ (pyrroloquinoline quinone), and ferric ion. Mechanistically it is a good model for BVR-A (biliverdin-IXalpha reductase), a potential pharmacological target for neonatal jaundice, and also a potential target for adjunct therapy to maintain protective levels of biliverdin-IXalpha during organ transplantation.[13]
Interactions
editBLVRB binds to human heme oxygenase-1 (hHO-1) in conjunction with cytochrome p450 reductase to catalyzes the NADPH-cytochrome P450 reductase-dependent oxidation of heme to biliverdin, CO, and free iron.[14]
References
edit- ^ a b c GRCh38: Ensembl release 89: ENSG00000090013 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040466 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: Biliverdin reductase B".
- ^ Saito F, Yamaguchi T, Komuro A, Tobe T, Ikeuchi T, Tomita M, Nakajima H (1995). "Mapping of the newly identified biliverdin-IX beta reductase gene (BLVRB) to human chromosome 19q13.13-->q13.2 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics. 71 (2): 179–81. doi:10.1159/000134102. PMID 7656592.
- ^ Yamaguchi T, Komuro A, Nakano Y, Tomita M, Nakajima H (Dec 1993). "Complete amino acid sequence of biliverdin-IX beta reductase from human liver". Biochemical and Biophysical Research Communications. 197 (3): 1518–23. doi:10.1006/bbrc.1993.2649. PMID 8280170.
- ^ Pereira PJ, Macedo-Ribeiro S, Párraga A, Pérez-Luque R, Cunningham O, Darcy K, Mantle TJ, Coll M (Mar 2001). "Structure of human biliverdin IXbeta reductase, an early fetal bilirubin IXbeta producing enzyme". Nature Structural Biology. 8 (3): 215–20. doi:10.1038/84948. PMID 11224564. S2CID 8276076.
- ^ Shalloe F, Elliott G, Ennis O, Mantle TJ (Jun 1996). "Evidence that biliverdin-IX beta reductase and flavin reductase are identical". The Biochemical Journal. 316 (2): 385–7. doi:10.1042/bj3160385. PMC 1217361. PMID 8687377.
- ^ Komuro A, Tobe T, Hashimoto K, Nakano Y, Yamaguchi T, Nakajima H, Tomita M (Jun 1996). "Molecular cloning and expression of human liver biliverdin-IX beta reductase". Biological & Pharmaceutical Bulletin. 19 (6): 796–804. doi:10.1248/bpb.19.796. PMID 8799475.
- ^ Yamaguchi T, Komoda Y, Nakajima H (Sep 1994). "Biliverdin-IX alpha reductase and biliverdin-IX beta reductase from human liver. Purification and characterization". The Journal of Biological Chemistry. 269 (39): 24343–8. doi:10.1016/S0021-9258(19)51088-2. PMID 7929092.
- ^ Cunningham O, Gore MG, Mantle TJ (Jan 2000). "Initial-rate kinetics of the flavin reductase reaction catalysed by human biliverdin-IXbeta reductase (BVR-B)". The Biochemical Journal. 345 (2): 393–9. doi:10.1042/bj3450393. PMC 1220769. PMID 10620517.
- ^ Smith LJ, Browne S, Mulholland AJ, Mantle TJ (May 2008). "Computational and experimental studies on the catalytic mechanism of biliverdin-IXbeta reductase" (PDF). The Biochemical Journal. 411 (3): 475–84. doi:10.1042/BJ20071495. PMID 18241201.
- ^ Wang J, de Montellano PR (May 2003). "The binding sites on human heme oxygenase-1 for cytochrome p450 reductase and biliverdin reductase". The Journal of Biological Chemistry. 278 (22): 20069–76. doi:10.1074/jbc.M300989200. PMID 12626517.
External links
edit- Human BLVRB genome location and BLVRB gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P30043 (Flavin reductase (NADPH)) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.