PDBsum entry 1he5

Biliverdin-ix beta reductase

PDB id: 1he5

Contents

Protein chain

205 a.a. *

Ligands

NAP

LUM

Waters ×271

* Residue conservation analysis

PDB id:

1he5

Name:

Biliverdin-ix beta reductase

Title:

Human biliverdin ix beta reductase: NADP/lumichrome ternary complex

Structure:

Biliverdin ix beta reductase. Chain: a. Synonym: flavin reductase (ec 1.6.99.1), NADPH-dependent diaphorase, NADPH-flavin reductase, biliverdin reductase b, green heme binding protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.50Å R-factor: 0.148 R-free: 0.192

Authors:

P.J.B.Pereira,S.Macedo-Ribeiro,A.Parraga,R.Perez-Luque,O.Cunningham, K.Darcy,T.J.Mantle,M.Coll

Key ref:

P.J.Pereira et al. (2001). Structure of human biliverdin IXbeta reductase, an early fetal bilirubin IXbeta producing enzyme. Nat Struct Biol, 8, 215-220. PubMed id: 11224564 DOI: 10.1038/84948

Date:

19-Nov-00 Release date: 28-Feb-01

Protein chain

P30043  (BLVRB_HUMAN) -  Flavin reductase (NADPH) from Homo sapiens

Seq: 206 a.a.

Struc: 205 a.a.

Enzyme reactions

• Enzyme class 2: E.C.1.3.1.- - ?????
• Enzyme class 3: E.C.1.5.1.30 - flavin reductase (NADPH).
• Reaction: reduced riboflavin + NADP⁺ = riboflavin + NADPH + 2 H⁺

reduced riboflavin (Bound ligand (Het Group name = NAP) corresponds exactly) + NADP(+) (Bound ligand (Het Group name = LUM) matches with 66.67% similarity) = riboflavin + NADPH + 2 × H(+)

• Enzyme class 4: E.C.2.6.99.- - ?????

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/84948

Nat Struct Biol 8:215-220 (2001)

PubMed id: 11224564

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

P.J.Pereira, S.Macedo-Ribeiro, A.Párraga, R.Pérez-Luque, O.Cunningham, K.Darcy, T.J.Mantle, M.Coll.

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.

Selected figure(s)

Figure 2.
Figure 2. Human BVR-B binds specifically to NADP. a, Stereo view of the NADP+ cofactor binding site. Putative hydrogen bonds are shown as dotted green lines, and solvent molecules as red spheres. The atom color code is the same as in Fig. 1b. The 1.15 Å 2F[o] - F[c] electron density map for the cofactor, contoured at 1.5 , is shown in blue. Residues interacting with NADP+ are numbered. b, Solid surface representation of human BVR-B in complex with NADP+ showing the wide substrate binding site adjacent to the cofactor. Electrostatic surface potentials are contoured from -10 (red) to 10 (blue) k[B]T e^-1. The cofactor carbon atoms are shown in white, phosphorous in yellow, nitrogens in blue and oxygens in red.

Figure 3.
Figure 3. Structural formulas of some human BVR-B substrates and inhibitors. a, FMN is a BVR-B substrate, lumichrome an inhibitor. b, Tetrapyrrole biliverdin IX , mesobiliverdin IV and 12-ethyl-13-methyl-mesobiliverdin IV are substrates; biliverdin IX is an inhibitor. The formation of a bilirubin isomer results from the reduction of C10 of the corresponding biliverdin (numbering as indicated for biliverdin IX , which is conserved for the bilatriene skeleton in all other isomers). The ring nomenclature for all -isomers is that shown for biliverdin IX .

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 215-220) copyright 2001.

Figures were selected by an automated process.