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xanthine dehydrogenase (XDH, XDHA)
Function:
- key enzyme in purine degradation
- catalyzes oxidation of hypoxanthine to xanthine
- catalyzes oxidation of xanthine to uric acid
- has low oxidase activity towards aldehydes (in vitro)
- can be converted from dehydrogenase form to the oxidase form (xanthine oxidase) irreversibly by proteolysis or reversibly through oxidation of sulfhydryl groups
- interacts with BTN1A1 (putative)
Xanthine + NAD+ + H2O urate + NADH
Xanthine + H2O + O2 urate + H2O2
Cofactor:
- binds 2 2Fe-2S clusters
- FAD
- molybdopterin
Structure:
- homodimer
- belongs to the xanthine dehydrogenase family
- contains 1 2Fe-2S ferredoxin-type domain
- contains 1 FAD-binding PCMH-type domain
Compartment: cytoplasm (putative), peroxisome, secreted
Expression: detected in milk (at protein level)
Pathology:
- defects in XDH are the cause of xanthinuria type 1
- may contribute to the generation of reactive oxygen species
- may contribute to adult respiratory stress syndrome (ARDS) & may potentiate influenza infection through an oxygen metabolite-dependent mechanism
Interactions
molecular events
Specific
xanthine oxidase
General
dehydrogenase
flavoprotein
human longevity protein
ketone oxidoreductase
metalloprotein
oligomerizing protein
phosphoprotein
Properties
SIZE: entity length = 1333 aa
MW = 146 kD
COMPARTMENT: peroxisome
cytoplasm
MOTIF: 2Fe-2S ferredoxin-type {4-91}
MOTIF: cofactor-binding site [43-43]
COFACTOR-BOUND: iron sulfur [FeS] cluster
cofactor-binding site [48-48]
COFACTOR-BOUND: iron sulfur [FeS] cluster
cofactor-binding site [51-51]
COFACTOR-BOUND: iron sulfur [FeS] cluster
cofactor-binding site [73-73]
COFACTOR-BOUND: iron sulfur [FeS] cluster
cofactor-binding site [113-113]
COFACTOR-BOUND: iron sulfur [FeS] cluster
cofactor-binding site [116-116]
COFACTOR-BOUND: iron sulfur [FeS] cluster
cofactor-binding site [148-148]
COFACTOR-BOUND: iron sulfur [FeS] cluster
cofactor-binding site [150-150]
COFACTOR-BOUND: iron sulfur [FeS] cluster
Thr phosphorylation site {T222}
binding site
SITE: 229-414
FOR-BINDING-OF: flavin adenine dinucleotide
MOTIF: cofactor-binding site [257-264]
COFACTOR-BOUND: flavin adenine dinucleotide
cofactor-binding site [337-337]
FOR-BINDING-OF: flavin adenine dinucleotide
cofactor-binding site [347-351]
COFACTOR-BOUND: flavin adenine dinucleotide
cofactor-binding site [360-360]
FOR-BINDING-OF: flavin adenine dinucleotide
cofactor-binding site [404-404]
FOR-BINDING-OF: flavin adenine dinucleotide
cofactor-binding site [422-422]
FOR-BINDING-OF: flavin adenine dinucleotide
cysteine residue {C509}
MODIFICATION: cysteine residue {C1318}
cysteine residue {C536}
MODIFICATION: cysteine residue {C993}
molybdenum [Mo]-pterin-binding site
SITE: 768-768
molybdenum [Mo]-pterin-binding site
SITE: 799-799
binding site
SITE: 803-803
FOR-BINDING-OF: Substrate
binding site
SITE: 881-881
FOR-BINDING-OF: Substrate
molybdenum [Mo]-pterin-binding site
SITE: 913-913
binding site
SITE: 915-915
FOR-BINDING-OF: Substrate
cysteine residue {C993}
MODIFICATION: cysteine residue {C536}
binding site
SITE: 1011-1011
FOR-BINDING-OF: Substrate
N-glycosylation site {N1074}
molybdenum [Mo]-pterin-binding site
SITE: 1080-1080
glutamate residue {E1262}
cysteine residue {C1318}
MODIFICATION: cysteine residue {C509}
Database Correlations
OMIM correlations
MORBIDMAP 607633
UniProt P47989
PFAM correlations
Entrez Gene 7498
Kegg hsa:7498
ENZYME correlations
References
- UniProt :accession P47989
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/XDH
- NIEHS-SNPs
http://egp.gs.washington.edu/data/xdh/
- UniProt PubMed refs
- PMID: 11379872
- PMID: 379872
- PMID: 9153281