Desulfo enzymes molybdenum

It is usually believed that NO inhibits enzymes by reacting with heme or nonheme iron or copper or via the S-nitrosilation or oxidation of sulfhydryl groups, although precise mechanisms are not always evident. By the use of ESR spectroscopy, Ichimori et al. [76] has showed that NO reacts with the sulfur atom coordinated to the xanthine oxidase molybdenum center, converting xanthine oxidase into a desulfo-type enzyme. Similarly, Sommer et al. [79] proposed that nitric oxide and superoxide inhibited calcineurin, one of the major serine and threonine phosphatases, by oxidation of metal ions or thiols. 

Figure 16-31 (A) Structure of molybdopterin cytosine dinucleotide complexed with an atom of molybdenum. (B) Stereoscopic ribbon drawing of the structure of one subunit of the xanthine oxidase-related aldehyde oxidoreductase from Desulfo-vibrio gigas. Each 907-residue subunit of the homodimeric protein contains two Fe2S2 clusters visible at the top and the molybdenum-molybdopterin coenzyme buried in the center. (C) Alpha-carbon plot of portions of the protein surrounding the molybdenum-molybdopterin cytosine dinucleotide and (at the top) the two plant-ferredoxin-like Fe2S2 clusters. Each of these is held by a separate structural domain of the protein. Two additional domains bind the molybdopterin coenzyme and there is also an intermediate connecting domain. In xanthine oxidase the latter presumably has the FAD binding site which is lacking in the D. gigas enzyme. From Romao et al.633 Courtesy of R. Huber.

The first hint of an essential role of molybdenum in metabolism came from the discovery that animals raised on a diet deficient in molybdenum had decreased liver xanthine oxidase activity. There is no evidence that xanthine oxidase is essential for all life, but a human genetic deficiency of sulfite oxidase or of its molybdopterin coenzyme can be lethal.646,646a,b The conversion of molybdate into the molybdopterin cofactor in E. coli depends upon at least five genes.677 In Drosophila the addition of the cyanolyzable sulfur (Eq. 16-64) is the final step in formation of xanthine dehydrogenase.678 It is of interest that sulfur (S°) can be transferred from rhodanese (see Eq. 24-45), or from a related mercaptopyruvate sulfurtransferase679 into the desulfo form of xanthine oxidase to generate an active enzyme.680... 

General Considerations. Much experimental information is available concerning the role of molybdenum in xanthine oxidase (19, 20). In early work (prior to 1970), there was much confusion in the literature because of the presence of various inactive forms of the enzyme. It is now known that both demolybdo and desulfo forms of xanthine oxidase were present in most early preparations and remain present in many current preparations as well (20, 64). 

A possibly more serious problem concerns recent EXAFS data on xanthine oxidase reported by Tullius et al (1979). In principle, the EXAFS method is capable of determining the nature of the ligand atoms in xanthine oxidase and of providing estimates of their distances from molybdenum. These workers suggested that there were two terminal oxygens in the enzyme but no terminal sulfur. Unfortunately, however, the enzyme sample which they used was a mixture of the functional and desulfo forms, and no attempt was made to separate the EXAFS spectra of the two species. One wonders whether the spectrum of desulfo xanthine oxidase could have been dominant. 

---