1LC0

Structure of Biliverdin Reductase and the Enzyme-NADH Complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.20 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.222 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal structure of a biliverdin IXalpha reductase enzyme-cofactor complex.

Whitby, F.G.Phillips, J.D.Hill, C.P.McCoubrey, W.Maines, M.D.

(2002) J Mol Biol 319: 1199-1210

  • DOI: https://doi.org/10.1016/S0022-2836(02)00383-2
  • Primary Citation of Related Structures:  
    1LC0, 1LC3

  • PubMed Abstract: 

    Biliverdin reductase (BVR) catalyzes the last step in heme degradation by reducing the gamma-methene bridge of the open tetrapyrrole, biliverdin IXalpha, to bilirubin with the concomitant oxidation of a beta-nicotinamide adenine dinucleotide (NADH) or beta-nicotinamide adenine dinucleotide phosphate (NADPH) cofactor. Bilirubin is the major bile pigment in mammals and has antioxidant and anticompliment activity. We have determined X-ray crystal structures of apo rat BVR and its complex with NADH at 1.2 A and 1.5 A resolution, respectively. In agreement with an independent structure determination of the apo-enzyme, BVR consists of an N-terminal dinucleotide-binding domain (Rossmann-fold) and a C-terminal domain that contains a six-stranded beta-sheet that is flanked on one face by several alpha-helices. The C-terminal and N-terminal domains interact extensively, forming the active site cleft at their interface. The cofactor complex structure reported here reveals that the cofactor nicotinamide ring extends into the active site cleft, where it is adjacent to conserved amino acid residues and, consistent with the known stereochemistry of the reaction catalyzed by BVR, the si face of the ring is accessible for hydride transfer. The only titratable side-chain that appears to be suitably positioned to function as a general acid in catalysis is Tyr97. This residue, however, is not essential for catalysis, since the Tyr97Phe mutant protein retains 50% activity. This finding suggests that the dominant role in catalysis may be performed by hydride transfer from the cofactor, a process that may be promoted by proximity of the invariant residues Glu96, Glu123, and Glu126, to the nicotinamide ring.


  • Organizational Affiliation

    Department of Biochemistry, University of Utah School of Medicine, 50 N. Medical Drive, Salt Lake City 84132, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Biliverdin Reductase A294Rattus norvegicusMutation(s): 0 
EC: 1.3.1.24
UniProt
Find proteins for P46844 (Rattus norvegicus)
Explore P46844 
Go to UniProtKB:  P46844
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP46844
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.20 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.222 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.78α = 90
b = 75.73β = 90
c = 76.08γ = 90
Software Package:
Software NamePurpose
SOLVEphasing
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-07-17
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations