Molybdenum cofactor domain

Wootton, J.C., Nicolson, R.E., Cock, J.M., Walters, D.E., Burke, J.F., Doyle, W.A. Bray, R.C. (1991). Enzymes depending on the pterin molybdenum cofactor sequence families, spectroscopic properties of molybdenum and possible cofactor-binding domains. Bio-chimica et Biophysica Acta 1057, 157-85. 

Mammalian XO is a homodimer of around 1330 amino acids which binds a number of electron transfer centres — an FAD, two spectroscopically distinct [2Fe-2S] clusters, and the Mo-cofactor. The structure of the bovine xanthine dehydrogenase (XDH), bound to the competitive inhibitor salicylic acid, and presented in Figure 17.3(a), consists of four domains, two Fe/S domains (1 and 11) in the N-terminal portion of the molecule, followed by the central FAD domain and the molybdenum-binding domain in the C-terminal part of the molecule. 

Peretz, H., Naamati, M. S., Levartovsky, D., Lagziel, A., Shani, E., Horn, I., Shalev, H., and Landau, D. (2007) Identification and characterization of the first mutation (Arg776Cys) in the C-terminal domain of the human molybdenum cofactor sulfurase (HMCS) associated with type II classical xanthinuria. Mol. Genet. Metab. 91 (1), 23-29. 

These enzymes may contain other redox-active sites (iron-sulfur centers, hemes, and/or flavins), either in distinct domains of a single polypeptide or bound in separate subunits. These additional cofactors perform electron transfer from the molybdenum center to an external electron acceptor/donor. 

Sulfite oxidase is a dimetallic enzyme that mediates the two-electron oxidation of sulfite by the one-electron reduction of cytochrome c. This reaction is physiologically essential as the terminal step in oxidative degradation of sulfur compounds. The enzyme contains a heme cofactor in the 10 kDa N-terminal domain and a molybdenum center in the 42 kDa C-terminal domain. The catalytic cycle is depicted in Fig. 9. 

Hydration and/or dehydration reactions are frequently catalyzed by metallopro-teins. Examples are proteins containing nickel (urease), zinc (e.g., peptidases), molybdenum (the hydratase partial reaction of formate oxidoreductase), tungsten (acetylene hydratase). An obvious difference between Ni, Zn, on the one hand, and Fe, Mo, W, on the other, is that the first are directly coordinated to the protein whereas the latter are also part of a cofactor. With reference to the Fe/S cluster in aconitase it has been suggested that cofactor coordination may provide an added flexibility to the active site, in particular to the substrate binding domain [15],... 

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