Primary Information
BoMiProt ID	Bomi23
Protein Name	Xanthine dehydrogenase/oxidase
Organism	Bos taurus
Uniprot ID	P80457
Milk Fraction	Whey
Ref Sequence ID	NP_776397.1
Aminoacid Length	1332
Molecular Weight	146790
FASTA Sequence	Download
Gene Name	XDH
Gene ID	280960
Protein Existence Status	Reviewed: Experimental evidence at protein level
Secondary Information
Presence in other biological fluids/tissue/cells	Blood, heart, liver, intestine, endothelial cells and at the luminal surface of rat liver sinusoidal endothelial cells,
Protein Function	catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid; source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various pathways; may induce mutagenesis, cell proliferation, and tumor progression, but they are also associated with apoptosis and cell differentiation; XOR activity generates free radicals and other oxidant reactive species resulting in either harmful or beneficial outcomes; modulate endothelial function and arteriolar tone; may be cytotoxic
Biochemical Properties	Represents more than 8% of the intrinsic protein in MFGM;homodimer; oxidizes in the presence of NAD+ or NADP+ as electron acceptors; bacterial XDHs usually show better catalytic activity and thermal stability than eukaryotic XDHs but both display optimum catalytic activity at nearly neutral pH and relatively low temperatures, and very limit pH-activity range; mammalian enzyme exists in two interconvertible forms, xanthine dehydrogenase and xanthine oxidase; can be interconverted reversibly by sulphide reagents or irreversibly by proteolysis; specificity is low for methylene blue and 2.6-dichlorophenolindophenol, ferricyanide, and many quinones; inactive forms are demolybdo or desulfo; XOR inhibitors are allopurinol, oxypurinol or analogues
Significance in milk	Antimicrobial activity; natural antibiotic; encourages breas-feeding in infants; generates hydrogen peroxide
PTMs	Bovine XOR is not glycosylated; human XO is N-glycosylated; goat MFGM XO contains sialic acids in O-linked glycosylation
Site(s) of PTM(s) N-glycosylation, O-glycosylation, Phosphorylation
SCOP	Class : All alpha proteins Fold : SWIRM/ISPC-type 4-helical bundle Superfamily : CO dehydrogenase ISP C-domain like Family : CO dehydrogenase ISP C-domain like Domain Name : 1VDV A:93-165 Class : Alpha and beta proteins (a+b) Fold : beta-Grasp Superfamily : 2Fe-2S ferredoxin-like Family : 2Fe-2S ferredoxin domains from multidomain proteins Domain Name : 1VDV A:3-92 Class : Alpha and beta proteins (a+b) Fold : alpha/beta-Hammerhead Superfamily : CO dehydrogenase molybdoprotein N-domain-like Family : CO dehydrogenase molybdoprotein N-domain-like Domain Name : 1VDV A:537-694 Class : Alpha and beta proteins (a+b) Fold : GSR C-terminal domain-like Superfamily : CO dehydrogenase flavoprotein C-terminal domain-like Family : CO dehydrogenase flavoprotein C-terminal domain-like Domain Name : 1VDV A:415-528 Class : Alpha and beta proteins (a+b) Fold : Molybdenum cofactor-binding domain Superfamily : Molybdenum cofactor-binding domain Family : Molybdenum cofactor-binding domain Domain Name : 1VDV A:695-1332
CATH	Matched CATH superfamily 1.10.150.120 3.30.365.10 3.30.390.50 3.30.43.10 3.30.465.10 3.90.1170.50 3.10.20.30
Predicted Disorder Regions	(166-191)
DisProt Annotation
TM Helix Prediction	No TM helices
PDB ID	1fiq, 1fo4, 1n5x, 1v97, 1vdv, 3am9, 3amz, 3ax7, 3ax9, 3b9j, 3bdj, 3etr, 3eub, 3nrz, 3ns1, 3nvv, 3nvw, 3nvy, 3nvz, 3sr6, 3una, 3unc, 3uni,
Additional Comments	XOR activity is upreglated in ischaemia that increases ROS; XOR production increases in brain meningitis;
Bibliography	1. Hancock, J. T., Salisbury, V., Ovejero-Boglione, M. C., Cherry, R., Hoare, C., Eisenthal, R., and Harrison, R. (2002) Antimicrobial properties of milk: dependence on presence of xanthine oxidase and nitrite. Antimicrob. Agents Chemother. 46, 3308–3310. 2. Wang, C.-H., Zhao, T.-X., Li, M., Zhang, C., and Xing, X.-H. (2016) Characterization of a novel Acinetobacter baumannii xanthine dehydrogenase expressed in Escherichia coli. Biotechnol. Lett. 38, 337–344. 3. Parks, D. A. and Granger, D. N. (1986) Xanthine oxidase: biochemistry, distribution and physiology. Acta Physiol. Scand. Suppl. 548, 87–99. 4. de Jong, J. W., van der Meer, P., Nieukoop, A. S., Huizer, T., Stroeve, R. J., and Bos, E. (1990) Xanthine oxidoreductase activity in perfused hearts of various species, including humans. Circ. Res. 67, 770–773. 5. Corte, E. D. and Stirpe, F. (1972) The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme. Biochem. J. 126, 739–745. 6. Bray, R. C. (1975) 6 Molybdenum Iron-Sulfur Flauin Hydroxylases and Related Enzymes. Enzym. 12, 299–419. 7. Gutteridge, S., Tanner, S. J., and Bray, R. C. (1978) Comparison of the molybdenum centres of native and desulpho xanthine oxidase. The nature of the cyanide-labile sulphur atom and the nature of the proton-accepting group. Biochem. J. 175, 887–897. 8. Wahl, R. C. and Rajagopalan, K. V. (1982) Evidence for the inorganic nature of the cyanolyzable sulfur of molybdenum hydroxylases. J. Biol. Chem. 257, 1354–1359. 9.Massey, V., Schopfer, L. M., Nishino, T., and Nishino, T. (1989) Differences in protein structure of xanthine dehydrogenase and xanthine oxidase revealed by reconstitution with flavin active site probes. J. Biol. Chem. 264, 10567–10573. 10. Miyamoto, Y., Akaike, T., Yoshida, M., Goto, S., Horie, H., and Maeda, H. (1996) Potentiation of nitric oxide-mediated vasorelaxation by xanthine oxidase inhibitors. Proc. Soc. Exp. Biol. Med. 211, 366–373. 11. Miyamoto, Y., Akaike, T., Yoshida, M., Goto, S., Horie, H., and Maeda, H. (1996) Potentiation of nitric oxide-mediated vasorelaxation by xanthine oxidase inhibitors. Proc. Soc. Exp. Biol. Med. 211, 366–373