1HE4

Human biliverdin IX beta reductase: NADP/FMN ternary complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.180 
  • R-Value Observed: 0.134 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Structure of Human Biliverdin Ix Beta Reductase, an Early Fetal Bilirubin Ix Producing Enzyme

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

(2001) Nat Struct Biol 8: 215

  • DOI: https://doi.org/10.1038/84948
  • Primary Citation of Related Structures:  
    1HDO, 1HE2, 1HE3, 1HE4, 1HE5

  • 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.


  • Organizational Affiliation

    Instituto de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Jordi Girona, 18-26, 08034 Barcelona, Spain.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BILIVERDIN IX BETA REDUCTASE206Homo sapiensMutation(s): 0 
EC: 1.3.1.24
UniProt & NIH Common Fund Data Resources
Find proteins for P30043 (Homo sapiens)
Explore P30043 
Go to UniProtKB:  P30043
PHAROS:  P30043
GTEx:  ENSG00000090013 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP30043
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAP
Query on NAP

Download Ideal Coordinates CCD File 
B [auth A]NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
FMN
Query on FMN

Download Ideal Coordinates CCD File 
C [auth A]FLAVIN MONONUCLEOTIDE
C17 H21 N4 O9 P
FVTCRASFADXXNN-SCRDCRAPSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.180 
  • R-Value Observed: 0.134 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 40.1α = 90
b = 49.3β = 90
c = 106.9γ = 90
Software Package:
Software NamePurpose
SHELXL-97refinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-02-28
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 2.0: 2019-05-22
    Changes: Advisory, Atomic model, Data collection, Other, Refinement description
  • Version 2.1: 2023-12-13
    Changes: Advisory, Data collection, Database references, Refinement description