Crystal structure and mechanism of action of the xanthine oxidase-related aldehyde oxidoreductase from Desulfovibrio gigas.

The crystal structure of the aldehyde oxidoreductase (Mop) from the sulphate-reducing bacterium Destdjovibrio gigas has been analysed and refined to 1.8A (0.18 nm) resolution in its native ‘desulpho’ form, as well as in ‘resulphurated’, oxidized, reduced and alcohol-bound forms [1,2], allowing a detailed look at several structural aspects relevant to catalysis. In analogy with eukaryotic xanthine oxidases, xanthine dehydrogenases and aldehyde oxidases, Mop is a homodimer of two 100 kDa subunits (2 x907 amino acids) [3] and it contains, per subunit, a molybdopterin cytosine dinucleotide (MCD) cofactor as well as two different kinds of [2Fe-2S] clusters [4], but lacks the flavin and its domain which is present in most molybdenum hydroxylases. It represents the first structure of a member of the xanthine oxidase family of enzymes, with the redox-active cofactors found in discrete domains within a single polypeptide chain. The molecule is roughly globular with an approximate diameter of 75 A and folds into four distinct domains (Fe/S-a, Fe/S-b, Mol and Mo2): the first two (Fe/S-a and Fe/S-b) bind the two iron-sulphur clusters, whereas the larger domains (Mol and Mo2) bind the MCD cofactor in extended conformation by a network of hydrogen-bonding interactions: Mol contributes with two single molybdopterin-binding segments and Mo2 binds the other side of the pterin system