3NVZ

Crystal Structure of Bovine Xanthine Oxidase in Complex with Indole-3-Aldehyde


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 

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This is version 1.3 of the entry. See complete history


Literature

Substrate orientation and specificity in xanthine oxidase: crystal structures of the enzyme in complex with indole-3-acetaldehyde and guanine.

Cao, H.Hall, J.Hille, R.

(2014) Biochemistry 53: 533-541

  • DOI: https://doi.org/10.1021/bi401465u
  • Primary Citation of Related Structures:  
    3NVW, 3NVZ

  • PubMed Abstract: 

    Xanthine oxidase is a molybdenum-containing hydroxylase that catalyzes the hydroxylation of sp(2)-hybridized carbon centers in a variety of aromatic heterocycles as well as aldehydes. Crystal structures of the oxidase form of the bovine enzyme in complex with a poor substrate indole-3-acetaldehyde and the nonsubstrate guanine have been determined, both at a resolution of 1.6 Å. In each structure, a specific and unambiguous orientation of the substrate in the active site is observed in which the hydroxylatable site is oriented away from the active site molybdenum center. The orientation seen with indole-3-acetaldehyde has the substrate positioned with the indole ring rather than the exocyclic aldehyde nearest the molybdenum center, indicating that the substrate must rotate some 30° in the enzyme active site to permit hydroxylation of the aldehyde group (as observed experimentally), accounting for the reduced reactivity of the enzyme toward this substrate. The principal product of hydroxylation of indole-3-acetaldehyde by the bovine enzyme is confirmed to be indole-3-carboxylic acid based on its characteristic UV-vis spectrum, and the kinetics of enzyme reduction are reported. With guanine, the dominant orientation seen crystallographically has the C-8 position that might be hydroxylated pointed away from the active site molybdenum center, in a configuration resembling that seen previously with hypoxanthine (a substrate that is effectively hydroxylated at position 2). The ∼180° reorientation required to permit reaction is sterically prohibited, indicating that substrate (mis)orientation in the active site is a major factor precluding formation of the highly mutagenic 8-hydroxyguanine.


  • Organizational Affiliation

    Department of Biochemistry, University of California , Riverside, California 92521, United States.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Xanthine dehydrogenase/oxidaseA,
D [auth J]
164Bos taurusMutation(s): 0 
EC: 1.17.1.4 (PDB Primary Data), 1.17.3.2 (PDB Primary Data)
UniProt
Find proteins for P80457 (Bos taurus)
Explore P80457 
Go to UniProtKB:  P80457
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP80457
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Xanthine dehydrogenase/oxidaseB,
E [auth K]
305Bos taurusMutation(s): 0 
EC: 1.17.1.4 (PDB Primary Data), 1.17.3.2 (PDB Primary Data)
UniProt
Find proteins for P80457 (Bos taurus)
Explore P80457 
Go to UniProtKB:  P80457
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP80457
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Xanthine dehydrogenase/oxidaseC,
F [auth L]
755Bos taurusMutation(s): 0 
EC: 1.17.1.4 (PDB Primary Data), 1.17.3.2 (PDB Primary Data)
UniProt
Find proteins for P80457 (Bos taurus)
Explore P80457 
Go to UniProtKB:  P80457
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP80457
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FAD
Query on FAD

Download Ideal Coordinates CCD File 
I [auth B],
O [auth K]
FLAVIN-ADENINE DINUCLEOTIDE
C27 H33 N9 O15 P2
VWWQXMAJTJZDQX-UYBVJOGSSA-N
MTE
Query on MTE

Download Ideal Coordinates CCD File 
J [auth C],
P [auth L]
PHOSPHONIC ACIDMONO-(2-AMINO-5,6-DIMERCAPTO-4-OXO-3,7,8A,9,10,10A-HEXAHYDRO-4H-8-OXA-1,3,9,10-TETRAAZA-ANTHRACEN-7-YLMETHYL)ESTER
C10 H14 N5 O6 P S2
HPEUEJRPDGMIMY-IFQPEPLCSA-N
FES
Query on FES

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G [auth A],
H [auth A],
M [auth J],
N [auth J]
FE2/S2 (INORGANIC) CLUSTER
Fe2 S2
NIXDOXVAJZFRNF-UHFFFAOYSA-N
MOS
Query on MOS

Download Ideal Coordinates CCD File 
K [auth C],
Q [auth L]
DIOXOTHIOMOLYBDENUM(VI) ION
H Mo O2 S
BDSRWPHSAKXXRG-UHFFFAOYSA-M
I3A
Query on I3A

Download Ideal Coordinates CCD File 
L [auth C],
R [auth L]
1H-INDOLE-3-CARBALDEHYDE
C9 H7 N O
OLNJUISKUQQNIM-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 133.409α = 90
b = 73.704β = 97.12
c = 138.922γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
MOSFLMdata reduction
SCALAdata scaling
CCP4phasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-01-19
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2014-09-03
    Changes: Database references
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations