Xanthine oxidase families molybdenum hydroxylases

Members of the xanthine oxidase family (i.e., the true hydroxylases) have molybdenum centers which consist of a single cofactor dithiolene ligand coordinated to a fac-MoOS-(H20) unit. Members of the sulfite oxidase family are likely to possess a single cofactor dithiolene coordinated to a cis M0O2 unit (additional coordination positions may be taken up by water and/or a cysteine residue that is conserved within the... 

Members of the xanthine oxidase family are regarded as molybdenum hydroxylases... 

The class of mononuclear molybdoenzymes can be divided into three groups based on the structure of their molybdenum centers (1) the xanthine oxidase family, which is the largest and most diverse family (the molybdenum hydroxylases) and catalyzes the hydroxylation of a broad range of aldehydes and... 

Different members of the xanthine oxidase family show differing susceptibility to cyanide. Thus, while mammalian aldehyde oxidases react more readily with cyanide, purine hydroxylase II imm Aspergillus nidulans was found to be highly resistant and only with extensive treatment did the desulfo form develop. Early XAS work indicated the presence of an oxo-sulfido active site with both Mo=0 and Mo=S coordination, and that the cyanolyzable sulfur is the Mo=S, and resolving a debate in which Mo=S and persulfide were candidates for the cyanolyzable sulfur. Xanthine oxidase also reacts with arsenite As(OH)3 to form an inhibited complex in which molybdenum is bound by arsenic through the labile sulfur (Mo-S-As). The conclusions of the early XAS study have recently been confirmed and extended by protein crystallography of the inhibitory species. ... 

Xanthine oxidase (XO) was the first enzyme studied from the family of enzymes now known as the molybdenum hydroxylases (HiUe 1999). XO, which catalyzes the hydroxylation of xanthine to uric acid is abundant in cow s milk and contains several cofactors, including FAD, two Fe-S centers, and a molybdenum cofactor, all of which are required for activity (Massey and Harris 1997). Purified XO has been shown to use xanthine, hypoxan-thine, and several aldehydes as substrates in the reduction of methylene blue (Booth 1938), used as an electron acceptor. Early studies also noted that cyanide was inhibitory but could only inactivate XO during preincubation, not during the reaction with xanthine (Dixon 1927). The target of cyanide inactivation was identified to be a labile sulfur atom, termed the cyanolyzable sulfur (Wahl and Rajagopalan 1982), which is also required for enzyme activity. 

Figure 11. Comparison of the EPR powder spectra (20 K) of the two reduced [2Fe2S] clusters FeSI and FeSII of various molybdenum hydroxylases of the xanthine oxidase (XO) family showing a pronounced variation of EPR parameters of the centers. The principal g-tensor components of both clusters are indicated. The horizontal arrows mark appearance of dipolar interaction between the clusters. The dashed rectangle covers the field range of sizeable contributions from paramagnetic Mo(V) species. Qor quinoline oxidoreductase Qox qui-naldine oxidase lor isoquinoline oxidoreductase Mop aldehyde oxidoreductase.

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