PDBsum entry 1fiq

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
164 a.a. *
305 a.a. *
745 a.a. *
FES ×2
Waters ×596
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of xanthine oxidase from bovine milk
Structure: Xanthine oxidase. Chain: a. Fragment: residues 1-219. Synonym: xo. Xanthine oxidase. Chain: b. Fragment: residues 220-569. Synonym: xo. Xanthine oxidase.
Source: Bos taurus. Cattle. Organism_taxid: 9913. Secretion: milk. Secretion: milk
Biol. unit: Hexamer (from PDB file)
2.50Å     R-factor:   0.212     R-free:   0.275
Authors: C.Enroth,B.T.Eger,K.Okamoto,T.Nishino,T.Nishino,E.F.Pai
Key ref:
C.Enroth et al. (2000). Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proc Natl Acad Sci U S A, 97, 10723-10728. PubMed id: 11005854 DOI: 10.1073/pnas.97.20.10723
04-Aug-00     Release date:   04-Oct-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P80457  (XDH_BOVIN) -  Xanthine dehydrogenase/oxidase
1332 a.a.
164 a.a.
Protein chain
Pfam   ArchSchema ?
P80457  (XDH_BOVIN) -  Xanthine dehydrogenase/oxidase
1332 a.a.
305 a.a.
Protein chain
Pfam   ArchSchema ?
P80457  (XDH_BOVIN) -  Xanthine dehydrogenase/oxidase
1332 a.a.
745 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chains A, B, C: E.C.  - Xanthine dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Xanthine Dehydrogenase
1. Xanthine + NAD+ + H2O = urate + NADH
2. Hypoxanthine + NAD+ + H2O = xanthine + NADH
Bound ligand (Het Group name = MTE)
matches with 45.83% similarity
+ NAD(+)
+ H(2)O
= urate
+ NAD(+)
+ H(2)O
Bound ligand (Het Group name = MTE)
matches with 45.83% similarity
      Cofactor: FAD; Iron-sulfur; Mo cation
Bound ligand (Het Group name = FAD) corresponds exactly
Mo cation
   Enzyme class 2: Chains A, B, C: E.C.  - Xanthine oxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: Xanthine + H2O + O2 = urate + H2O2
+ H(2)O
+ O(2)
= urate
+ H(2)O(2)
      Cofactor: FAD; Iron-sulfur; Molybdopterin
Bound ligand (Het Group name = FAD) corresponds exactly
Bound ligand (Het Group name = MTE) corresponds exactly
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   1 term 
  Biochemical function     electron carrier activity     10 terms  


DOI no: 10.1073/pnas.97.20.10723 Proc Natl Acad Sci U S A 97:10723-10728 (2000)
PubMed id: 11005854  
Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion.
C.Enroth, B.T.Eger, K.Okamoto, T.Nishino, T.Nishino, E.F.Pai.
Mammalian xanthine oxidoreductases, which catalyze the last two steps in the formation of urate, are synthesized as the dehydrogenase form xanthine dehydrogenase (XDH) but can be readily converted to the oxidase form xanthine oxidase (XO) by oxidation of sulfhydryl residues or by proteolysis. Here, we present the crystal structure of the dimeric (M(r), 290,000) bovine milk XDH at 2.1-A resolution and XO at 2.5-A resolution and describe the major changes that occur on the proteolytic transformation of XDH to the XO form. Each molecule is composed of an N-terminal 20-kDa domain containing two iron sulfur centers, a central 40-kDa flavin adenine dinucleotide domain, and a C-terminal 85-kDa molybdopterin-binding domain with the four redox centers aligned in an almost linear fashion. Cleavage of surface-exposed loops of XDH causes major structural rearrangement of another loop close to the flavin ring (Gln 423Lys 433). This movement partially blocks access of the NAD substrate to the flavin adenine dinucleotide cofactor and changes the electrostatic environment of the active site, reflecting the switch of substrate specificity observed for the two forms of this enzyme.
  Selected figure(s)  
Figure 2.
Fig. 2. Stereo representation of salicylate as bound in the Mo-pt active site of XDH plus corresponding 2F[o]-F[c] electron density contoured at 1 cutoff. Cofactor, inhibitor, the two sandwiching residues Phe 914 and Phe 1009, and Glu 1261 are labeled.
Figure 3.
Fig. 3. FAD- and Fe/S II-binding sites of XDH. The view is into the cleft toward the si-site of the flavin ring. Several amino acids are drawn in ball-and-stick mode: Thr 262, Glu 45, and Gly 48, whose main chain carbonyl atoms are close to the 7 - and 8 -methyl groups of the flavin ring; Phe 337 in stacking interaction with the re-side of the pyrimidine part of the flavin ring; Asp 429, whose side chain lies in plane with the flavin and only 3.6 Å from its C6 atom; Arg 426, whose side chain becomes the one closest to the flavin ring in XO.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

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PDB code: 3etr
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The Mo-Se active site of nicotinate dehydrogenase.
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PDB code: 3hrd
18678861 A.Papi, M.Contoli, P.Gasparini, L.Bristot, M.R.Edwards, M.Chicca, M.Leis, A.Ciaccia, G.Caramori, S.L.Johnston, and S.Pinamonti (2008).
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18300946 M.Kudo, T.Moteki, T.Sasaki, Y.Konno, S.Ujiie, A.Onose, M.Mizugaki, M.Ishikawa, and M.Hiratsuka (2008).
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PDB code: 3l4p
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Structure of the non-redox-active tungsten/[4Fe:4S] enzyme acetylene hydratase.
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PDB code: 2e7z
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To be or not to be an oxidase: challenging the oxygen reactivity of flavoenzymes.
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Molybdenum and tungsten enzymes: the xanthine oxidase family.
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Electrochemistry of xanthine oxidase and its interaction with nitric oxide.
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Macromolecular crowding enhances the binding of superoxide dismutase to xanthine oxidase: implications for protein-protein interactions in intracellular environments.
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Active site geometry and substrate recognition of the molybdenum hydroxylase quinoline 2-oxidoreductase.
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PDB code: 1t3q
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The crystal structure of xanthine oxidoreductase during catalysis: implications for reaction mechanism and enzyme inhibition.
  Proc Natl Acad Sci U S A, 101, 7931-7936.
PDB code: 1v97
15576037 M.Unciuleac, E.Warkentin, C.C.Page, M.Boll, and U.Ermler (2004).
Structure of a xanthine oxidase-related 4-hydroxybenzoyl-CoA reductase with an additional [4Fe-4S] cluster and an inverted electron flow.
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PDB codes: 1rm6 1sb3
14576276 F.Rodríguez-Trelles, R.Tarrío, and F.J.Ayala (2003).
Convergent neofunctionalization by positive Darwinian selection after ancient recurrent duplications of the xanthine dehydrogenase gene.
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12655066 H.K.Joshi, J.J.Cooney, F.E.Inscore, N.E.Gruhn, D.L.Lichtenberger, and J.H.Enemark (2003).
Investigation of metal-dithiolate fold angle effects: implications for molybdenum and tungsten enzymes.
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Deflavination and reconstitution of flavoproteins.
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Factors involved in the assembly of a functional molybdopyranopterin center in recombinant Comamonas acidovorans xanthine dehydrogenase.
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Unique amino acids cluster for switching from the dehydrogenase to oxidase form of xanthine oxidoreductase.
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Production of aldehyde oxidases by microorganisms and their enzymatic properties.
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The housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland.
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Catalysis at a dinuclear [CuSMo(==O)OH] cluster in a CO dehydrogenase resolved at 1.1-A resolution.
  Proc Natl Acad Sci U S A, 99, 15971-15976.
PDB codes: 1n5w 1n60 1n61 1n62 1n63
12220497 H.Raaijmakers, S.Macieira, J.M.Dias, S.Teixeira, S.Bursakov, R.Huber, J.J.Moura, I.Moura, and M.J.Romão (2002).
Gene sequence and the 1.8 A crystal structure of the tungsten-containing formate dehydrogenase from Desulfovibrio gigas.
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PDB code: 1h0h
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Serum xanthine oxidase: origin, regulation, and contribution to control of trypanosome parasitemia.
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The skeletal muscle Ca2+ release channel has an oxidoreductase-like domain.
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Structure and function of xanthine oxidoreductase: where are we now?
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Molybdenum and tungsten in biology.
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Urate produced during hypoxia protects heart proteins from peroxynitrite-mediated protein nitration.
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The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.