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PDBsum entry 1jrp

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1jrp
Jmol
Contents
Protein chains
450 a.a. *
760 a.a. *
Ligands
FES ×8
MPN-MOS ×4
FAD ×4
141 ×4
Metals
_CA ×4
* Residue conservation analysis
PDB id:
1jrp
Name: Oxidoreductase
Title: Crystal structure of xanthine dehydrogenase inhibited by alloxanthine from rhodobacter capsulatus
Structure: Xanthine dehydrogenase, chain a. Chain: a, c, e, g. Fragment: chain a, residues 1-462. Synonym: xd. Engineered: yes. Xanthine dehydrogenase, chain b. Chain: b, d, f, h. Fragment: chain b, residues 1-777. Synonym: xd.
Source: Rhodobacter capsulatus. Organism_taxid: 1061. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Hexamer (from PQS)
Resolution:
3.00Å     R-factor:   0.196     R-free:   0.243
Authors: J.J.Truglio,K.Theis,S.Leimkuhler,R.Rappa,K.V.Rajagopalan, C.Kisker
Key ref:
J.J.Truglio et al. (2002). Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus. Structure, 10, 115-125. PubMed id: 11796116 DOI: 10.1016/S0969-2126(01)00697-9
Date:
14-Aug-01     Release date:   11-Jan-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O54050  (O54050_RHOCA) -  Xanthine dehydrogenase
Seq:
Struc:
462 a.a.
450 a.a.
Protein chains
Pfam   ArchSchema ?
O54051  (O54051_RHOCA) -  Xanthine dehydrogenase
Seq:
Struc:
 
Seq:
Struc:
777 a.a.
760 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F, G, H: E.C.1.1.1.204  - Transferred entry: 1.17.1.4.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Xanthine + NAD+ + H2O = urate + NADH

Bound ligand (Het Group name = MPN)
matches with 45.00% similarity
+

Bound ligand (Het Group name = FAD)
matches with 76.00% similarity
+
=
+
      Cofactor: Molybdenum
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     catalytic activity     13 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(01)00697-9 Structure 10:115-125 (2002)
PubMed id: 11796116  
 
 
Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus.
J.J.Truglio, K.Theis, S.Leimkühler, R.Rappa, K.V.Rajagopalan, C.Kisker.
 
  ABSTRACT  
 
Xanthine dehydrogenase (XDH), a complex molybdo/iron-sulfur/flavoprotein, catalyzes the oxidation of hypoxanthine to xanthine followed by oxidation of xanthine to uric acid with concomitant reduction of NAD+. The 2.7 A resolution structure of Rhodobacter capsulatus XDH reveals that the bacterial and bovine XDH have highly similar folds despite differences in subunit composition. The NAD+ binding pocket of the bacterial XDH resembles that of the dehydrogenase form of the bovine enzyme rather than that of the oxidase form, which reduces O(2) instead of NAD+. The drug allopurinol is used to treat XDH-catalyzed uric acid build-up occurring in gout or during cancer chemotherapy. As a hypoxanthine analog, it is oxidized to alloxanthine, which cannot be further oxidized but acts as a tight binding inhibitor of XDH. The 3.0 A resolution structure of the XDH-alloxanthine complex shows direct coordination of alloxanthine to the molybdenum via a nitrogen atom. These results provide a starting point for the rational design of new XDH inhibitors.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Schematic Representation of Protein-Moco InteractionsDashed lines indicate hydrogen bonds. In addition, the aromatic side chain of Phe-B228 stacks with the pterin rings (not shown).
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 115-125) copyright 2002.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21151514 M.Neumann, and S.Leimkühler (2011).
The role of system-specific molecular chaperones in the maturation of molybdoenzymes in bacteria.
  Biochem Res Int, 2011, 850924.  
19828843 M.C.Gomez-Cabrera, G.L.Close, A.Kayani, A.McArdle, J.Viña, and M.J.Jackson (2010).
Effect of xanthine oxidase-generated extracellular superoxide on skeletal muscle force generation.
  Am J Physiol Regul Integr Comp Physiol, 298, R2-R8.  
20053956 Y.Fu, R.Zhang, D.Lu, H.Liu, K.Chandrashekar, L.A.Juncos, and R.Liu (2010).
NOX2 is the primary source of angiotensin II-induced superoxide in the macula densa.
  Am J Physiol Regul Integr Comp Physiol, 298, R707-R712.  
19675644 G.Schwarz, R.R.Mendel, and M.W.Ribbe (2009).
Molybdenum cofactors, enzymes and pathways.
  Nature, 460, 839-847.  
19109252 J.M.Pauff, H.Cao, and R.Hille (2009).
Substrate Orientation and Catalysis at the Molybdenum Site in Xanthine Oxidase: CRYSTAL STRUCTURES IN COMPLEX WITH XANTHINE AND LUMAZINE.
  J Biol Chem, 284, 8760-8767.  
19388706 J.M.Pauff, and R.Hille (2009).
Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin.
  J Nat Prod, 72, 725-731.  
19452052 M.J.Romão (2009).
Molybdenum and tungsten enzymes: a crystallographic and mechanistic overview.
  Dalton Trans, (), 4053-4068.  
19401776 S.Schumann, M.Terao, E.Garattini, M.Saggu, F.Lendzian, P.Hildebrandt, and S.Leimkühler (2009).
Site directed mutagenesis of amino acid residues at the active site of mouse aldehyde oxidase AOX1.
  PLoS ONE, 4, e5348.  
19109249 U.Dietzel, J.Kuper, J.A.Doebbler, A.Schulte, J.J.Truglio, S.Leimkühler, and C.Kisker (2009).
Mechanism of Substrate and Inhibitor Binding of Rhodobacter capsulatus Xanthine Dehydrogenase.
  J Biol Chem, 284, 8768-8776.
PDB codes: 2w3r 2w3s 2w54 2w55
18063585 J.M.Pauff, J.Zhang, C.E.Bell, and R.Hille (2008).
Substrate orientation in xanthine oxidase: crystal structure of enzyme in reaction with 2-hydroxy-6-methylpurine.
  J Biol Chem, 283, 4818-4824.
PDB code: 3b9j
18036331 M.Li, T.A.Müller, B.A.Fraser, and R.P.Hausinger (2008).
Characterization of active site variants of xanthine hydroxylase from Aspergillus nidulans.
  Arch Biochem Biophys, 470, 44-53.  
18354776 S.Chaves, M.Gil, S.Canário, R.Jelic, M.J.Romão, J.Trincão, E.Herdtweck, J.Sousa, C.Diniz, P.Fresco, and M.A.Santos (2008).
Biologically relevant O,S-donor compounds. Synthesis, molybdenum complexation and xanthine oxidase inhibition.
  Dalton Trans, (), 1773-1782.  
18390908 S.Schumann, M.Saggu, N.Möller, S.D.Anker, F.Lendzian, P.Hildebrandt, and S.Leimkühler (2008).
The mechanism of assembly and cofactor insertion into Rhodobacter capsulatus xanthine dehydrogenase.
  J Biol Chem, 283, 16602-16611.  
18513323 T.Nishino, K.Okamoto, B.T.Eger, E.F.Pai, and T.Nishino (2008).
Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase.
  FEBS J, 275, 3278-3289.  
17605815 A.M.Burroughs, S.Balaji, L.M.Iyer, and L.Aravind (2007).
Small but versatile: the extraordinary functional and structural diversity of the beta-grasp fold.
  Biol Direct, 2, 18.  
17139522 A.Thapper, D.R.Boer, C.D.Brondino, J.J.Moura, and M.J.Romão (2007).
Correlating EPR and X-ray structural analysis of arsenite-inhibited forms of aldehyde oxidoreductase.
  J Biol Inorg Chem, 12, 353-366.
PDB code: 3l4p
17429948 G.M.Montero-Morán, M.Li, E.Rendòn-Huerta, F.Jourdan, D.J.Lowe, A.W.Stumpff-Kane, M.Feig, C.Scazzocchio, and R.P.Hausinger (2007).
Purification and characterization of the FeII- and alpha-ketoglutarate-dependent xanthine hydroxylase from Aspergillus nidulans.
  Biochemistry, 46, 5293-5304.  
17327224 J.M.Pauff, C.F.Hemann, N.Jünemann, S.Leimkühler, and R.Hille (2007).
The role of arginine 310 in catalysis and substrate specificity in xanthine dehydrogenase from Rhodobacter capsulatus.
  J Biol Chem, 282, 12785-12790.  
17600788 K.Pal, P.K.Chaudhury, and S.Sarkar (2007).
Structure of the Michaelis complex and function of the catalytic center in the reductive half-reaction of computational and synthetic models of sulfite oxidase.
  Chem Asian J, 2, 956-964.  
16480912 C.D.Brondino, M.J.Romão, I.Moura, and J.J.Moura (2006).
Molybdenum and tungsten enzymes: the xanthine oxidase family.
  Curr Opin Chem Biol, 10, 109-114.  
16597619 M.Neumann, M.Schulte, N.Jünemann, W.Stöcklein, and S.Leimkühler (2006).
Rhodobacter capsulatus XdhC is involved in molybdenum cofactor binding and insertion into xanthine dehydrogenase.
  J Biol Chem, 281, 15701-15708.  
16507884 P.Pacher, A.Nivorozhkin, and C.Szabó (2006).
Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol.
  Pharmacol Rev, 58, 87.  
  16508115 D.R.Boer, A.Müller, S.Fetzner, D.J.Lowe, and M.J.Romão (2005).
On the purification and preliminary crystallographic analysis of isoquinoline 1-oxidoreductase from Brevundimonas diminuta 7.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 137-140.  
15937278 H.Cheng, and N.V.Grishin (2005).
DOM-fold: a structure with crossing loops found in DmpA, ornithine acetyltransferase, and molybdenum cofactor-binding domain.
  Protein Sci, 14, 1902-1910.  
15863498 U.Kappler, and S.Bailey (2005).
Molecular basis of intramolecular electron transfer in sulfite-oxidizing enzymes is revealed by high resolution structure of a heterodimeric complex of the catalytic molybdopterin subunit and a c-type cytochrome subunit.
  J Biol Chem, 280, 24999-25007.
PDB codes: 2blf 2bpb
14694147 C.E.Berry, and J.M.Hare (2004).
Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications.
  J Physiol, 555, 589-606.  
15296736 I.Bonin, B.M.Martins, V.Purvanov, S.Fetzner, R.Huber, and H.Dobbek (2004).
Active site geometry and substrate recognition of the molybdenum hydroxylase quinoline 2-oxidoreductase.
  Structure, 12, 1425-1435.
PDB code: 1t3q
15311335 J.J.Moura, C.D.Brondino, J.Trincão, and M.J.Romão (2004).
Mo and W bis-MGD enzymes: nitrate reductases and formate dehydrogenases.
  J Biol Inorg Chem, 9, 791-799.  
15355966 L.Loschi, S.J.Brokx, T.L.Hills, G.Zhang, M.G.Bertero, A.L.Lovering, J.H.Weiner, and N.C.Strynadka (2004).
Structural and biochemical identification of a novel bacterial oxidoreductase.
  J Biol Chem, 279, 50391-50400.
PDB codes: 1xdq 1xdy
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.
  Structure, 12, 2249-2256.
PDB codes: 1rm6 1sb3
15265866 S.Leimkühler, A.L.Stockert, K.Igarashi, T.Nishino, and R.Hille (2004).
The role of active site glutamate residues in catalysis of Rhodobacter capsulatus xanthine dehydrogenase.
  J Biol Chem, 279, 40437-40444.  
12730200 K.Parschat, B.Hauer, R.Kappl, R.Kraft, J.Huttermann, and S.Fetzner (2003).
Gene cluster of Arthrobacter ilicis Ru61a involved in the degradation of quinaldine to anthranilate: characterization and functional expression of the quinaldine 4-oxidase qoxLMS genes.
  J Biol Chem, 278, 27483-27494.  
14622263 N.V.Ivanov, F.Hubálek, M.Trani, and D.E.Edmondson (2003).
Factors involved in the assembly of a functional molybdopyranopterin center in recombinant Comamonas acidovorans xanthine dehydrogenase.
  Eur J Biochem, 270, 4744-4754.  
12670960 S.Leimkuhler, R.Hodson, G.N.George, and K.V.Rajagopalan (2003).
Recombinant Rhodobacter capsulatus xanthine dehydrogenase, a useful model system for the characterization of protein variants leading to xanthinuria I in humans.
  J Biol Chem, 278, 20802-20811.  
12114025 R.Hille (2002).
Molybdenum and tungsten in biology.
  Trends Biochem Sci, 27, 360-367.  
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 codes are shown on the right.