3AX9

Bovine xanthine oxidase, protease cleaved form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.218 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Protein conformational gating of enzymatic activity in xanthine oxidoreductase

Ishikita, H.Eger, B.T.Okamoto, K.Nishino, T.Pai, E.F.

(2012) J Am Chem Soc 134: 999-1009

  • DOI: https://doi.org/10.1021/ja207173p
  • Primary Citation of Related Structures:  
    3AX7, 3AX9, 3UNA, 3UNC, 3UNI

  • PubMed Abstract: 

    In mammals, xanthine oxidoreductase can exist as xanthine dehydrogenase (XDH) and xanthine oxidase (XO). The two enzymes possess common redox active cofactors, which form an electron transfer (ET) pathway terminated by a flavin cofactor. In spite of identical protein primary structures, the redox potential difference between XDH and XO for the flavin semiquinone/hydroquinone pair (E(sq/hq)) is ~170 mV, a striking difference. The former greatly prefers NAD(+) as ultimate substrate for ET from the iron-sulfur cluster FeS-II via flavin while the latter only accepts dioxygen. In XDH (without NAD(+)), however, the redox potential of the electron donor FeS-II is 180 mV higher than that for the acceptor flavin, yielding an energetically uphill ET. On the basis of new 1.65, 2.3, 1.9, and 2.2 Å resolution crystal structures for XDH, XO, the NAD(+)- and NADH-complexed XDH, E(sq/hq) were calculated to better understand how the enzyme activates an ET from FeS-II to flavin. The majority of the E(sq/hq) difference between XDH and XO originates from a conformational change in the loop at positions 423-433 near the flavin binding site, causing the differences in stability of the semiquinone state. There was no large conformational change observed in response to NAD(+) binding at XDH. Instead, the positive charge of the NAD(+) ring, deprotonation of Asp429, and capping of the bulk surface of the flavin by the NAD(+) molecule all contribute to altering E(sq/hq) upon NAD(+) binding to XDH.


  • Organizational Affiliation

    Career-Path Promotion Unit for Young Life Scientists, Kyoto University, 202 Building E, Graduate School of Medicine, Kyoto 606-8501, Japan. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Xanthine dehydrogenase/oxidase
A, B
1,332Bos 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
Expand
  • Reference Sequence
Small Molecules
Ligands 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FAD
Query on FAD

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

Download Ideal Coordinates CCD File 
F [auth A],
P [auth B]
{[(5aR,8R,9aR)-2-amino-4-oxo-6,7-di(sulfanyl-kappaS)-3,5,5a,8,9a,10-hexahydro-4H-pyrano[3,2-g]pteridin-8-yl]methyl dihydrogenato(2-) phosphate}(hydroxy)oxo(thioxo)molybdenum
C10 H13 Mo N5 O8 P S3
OIQYCPXIZLGKQT-BKZHXLINSA-K
FES
Query on FES

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
M [auth B],
N [auth B]
FE2/S2 (INORGANIC) CLUSTER
Fe2 S2
NIXDOXVAJZFRNF-UHFFFAOYSA-N
SAL
Query on SAL

Download Ideal Coordinates CCD File 
L [auth A],
U [auth B]
2-HYDROXYBENZOIC ACID
C7 H6 O3
YGSDEFSMJLZEOE-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
I [auth A],
J [auth A],
K [auth A],
S [auth B],
T [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
BCT
Query on BCT

Download Ideal Coordinates CCD File 
H [auth A],
R [auth B]
BICARBONATE ION
C H O3
BVKZGUZCCUSVTD-UHFFFAOYSA-M
CA
Query on CA

Download Ideal Coordinates CCD File 
G [auth A],
Q [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SAL BindingDB:  3AX9 Ki: 1.00e+8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.218 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 133.196α = 90
b = 72.966β = 98.84
c = 142.261γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-02-22
    Type: Initial release
  • Version 1.1: 2013-09-25
    Changes: Structure summary
  • Version 1.2: 2024-03-13
    Changes: Data collection, Database references, Derived calculations