3UNA

Crystal Structure of Bovine Milk Xanthine Dehydrogenase with NAD Bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.214 
  • R-Value Work: 0.181 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.1 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 9 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FAD
Query on FAD

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

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H [auth A],
Y [auth B]
NICOTINAMIDE-ADENINE-DINUCLEOTIDE
C21 H27 N7 O14 P2
BAWFJGJZGIEFAR-NNYOXOHSSA-N
MTE
Query on MTE

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E [auth A],
V [auth B]
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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C [auth A],
D [auth A],
T [auth B],
U [auth B]
FE2/S2 (INORGANIC) CLUSTER
Fe2 S2
NIXDOXVAJZFRNF-UHFFFAOYSA-N
MOS
Query on MOS

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F [auth A],
W [auth B]
DIOXOTHIOMOLYBDENUM(VI) ION
H Mo O2 S
BDSRWPHSAKXXRG-UHFFFAOYSA-M
SAL
Query on SAL

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AA [auth B],
J [auth A]
2-HYDROXYBENZOIC ACID
C7 H6 O3
YGSDEFSMJLZEOE-UHFFFAOYSA-N
GOL
Query on GOL

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BA [auth B]
CA [auth B]
DA [auth B]
EA [auth B]
FA [auth B]
BA [auth B],
CA [auth B],
DA [auth B],
EA [auth B],
FA [auth B],
K [auth A],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A],
R [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
CO3
Query on CO3

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I [auth A],
Z [auth B]
CARBONATE ION
C O3
BVKZGUZCCUSVTD-UHFFFAOYSA-L
CA
Query on CA

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GA [auth B],
S [auth A]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SAL BindingDB:  3UNA Ki: 1.00e+8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.214 
  • R-Value Work: 0.181 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 166.028α = 90
b = 123.182β = 91.02
c = 147.624γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
EPMRphasing
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-05-09
    Type: Initial release
  • Version 1.1: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description