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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the basis of the crystal structure of an aldehyde oxidoreductase, Huber et al. proposed a catalytic mechanism for the reductive half-reaction of xanthine oxidase which involves nucleophilic addition of Mo-bound hydroxide (Moco 1) to the substrate and hydride transfer from the substrate to sulfido group (Mo=S). Density functional theory calculations have been carried out for the oxidation of formaldehyde, acetaldehyde, formamide, and formamidine with Moco 2 to understand more detailed catalytic pathways. Our calculation results indicate that the anionic catalyst model acts as a nucleophile and is reactive for the oxidation of aldehyde substrates, which are reactive for nucleophilic addition. In these cases, a concerted mechanism is found to be more favorable than a stepwise mechanism. The concerted mechanism is further shown to be promoted by the presence of a nearby water molecule, in the active site, which serves as a Lewis acid for the nucleophilic addition of hydroxide. For less reactive formamide and formamidine (a model for xanthine) substrates, the calculated activation energies with the above mechanisms are high. These reactions also do not benefit from the presence of the water molecule. The results indicate that different catalyst forms might be responsible for the oxidation of different substrates, which could be regulated by the enzyme active site environment.
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PMID:A theoretical study on the mechanism of the reductive half-reaction of xanthine oxidase. 1573 88

Synthesis of two complexes, [NBu(n)(4)][Mo(IV)O(mnt)(S-Tol)(N-N)] (N-N = 2,2'-bipyridine (1a) or 1,10-phenanthroline (1b); mnt = maleonitriledithiolate; S-Tol = toluenethiol) are reported. These on treatment with H(2)S generate the corresponding [NBu(n)(4)][Mo(IV)O(mnt)(SH)(N-N)] (2a and 2b) complexes bearing the susceptible hydrosulfide coordination. 2a (and 2b) upon chemical oxidation show EPR spectra with the appearance of a Mo(V) signal at <g> = 1.976 (for 2a and 2b). Such EPR signal changed to another slow Mo(V) signal at <g> = 1.949 at the expense of the initial signal. This conversion is accelerated in the presence of trace amount of moisture in the solvent. These data are similar to the Moco isolated from the xanthine oxidase (XO) as reported by Bray. 2a (and 2b) responds to one electron electrochemical oxidation and the generated pentavalent species responds to proton coupled electron transfer reaction. A predominantly metal centered HOMO is observed in 2a (and 2b) from DFT calculations. In the inhibited Moco of XO bearing a -SH moiety, the HOMO shows considerably less electron density residing on the Mo d(xy) orbital and maximum electron density is distributed to the phospho-ester group rendering the Mo(IV) center incapable of participating in the electron transfer process manifesting inhibition.
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PMID:Modelling the reduced xanthine oxidase in active sulfo and inactive desulfo forms. 2329 56

The last 20 years have seen a dramatic increase in our mechanistic understanding of the reactions catalyzed by pyranopterin Mo and W enzymes. These enzymes possess a unique cofactor (Moco) that contains a novel ligand in bioinorganic chemistry, the pyranopterin ene-1,2-dithiolate. A synopsis of Moco biosynthesis and structure is presented, along with our current understanding of the role Moco plays in enzymatic catalysis. Oxygen atom transfer (OAT) reactivity is discussed in terms of breaking strong metal-oxo bonds and the mechanism of OAT catalyzed by enzymes of the sulfite oxidase (SO) family that possess dioxo Mo(VI) active sites. OAT reactivity is also discussed in members of the dimethyl sulfoxide (DMSO) reductase family, which possess des-oxo Mo(IV) sites. Finally, we reveal what is known about hydride transfer reactivity in xanthine oxidase (XO) family enzymes and the formate dehydrogenases. The formal hydride transfer reactivity catalyzed by xanthine oxidase family enzymes is complex and cleaves substrate C-H bonds using a mechanism that is distinct from monooxygenases. The chapter primarily highlights developments in the field that have occurred since ~2000, which have contributed to our collective structural and mechanistic understanding of the three canonical pyranopterin Mo enzymes families: XO, SO, and DMSO reductase.
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PMID:Molybdenum and Tungsten Cofactors and the Reactions They Catalyze. 3285 30