Molybdenum hydroxylases structure

In this section are described the important chemical features of those substrates which are oxidized by the molybdenum hydroxylases. Although these enzymes, particularly aldehyde oxidase, also catalyse numerous reductive reactions under anaerobic conditions in vitro, it has not yet been established whether they occur under physiological conditions and there are as yet insufficient examples of any one reduction reaction to permit any conclusions regarding the structure of substrates. Thus, such reactions will not be discussed here (see [11] and references therein). Properties of those inhibitors which bind at the Mo centre and are also substrate analogues will also be included. However, the interaction of inhibitors such as cyanide and arsenite with the molybdenum hydroxylases and the mechanism of action of the specific xanthine oxidase inhibitor, allo-purinol, have been comprehensively described elsewhere [8, 12, 14, 157]. 

In spite of the close structural relationship of the molybdenum hydroxylases, including a tendency for hydrophobic substrate/enzyme interaction, there is a very significant difference in the substrate specificity of the two enzymes. Not only is there considerable variation in the affinities for substrates and inhibitors, but there is often a difference in the position of oxidative attack. As both enzymes catalyse apparently similar nucleophilic reactions, this difference cannot be explained solely from electronic considerations and is probably due, to a great extent, to the differential response of each enzyme to steric factors. 

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... 

Of all of the molybdenum enzymes, mammalian xanthine oxidase/dehydrogenase has been the most studied (Figure 15). These studies, along with those of other members of this relatively large class of hydroxylases (Table la-c), suggest that all molybdenum enzymes that catalyze hydroxylation of C—H bonds contain a common structural motif. This motif is unique in high-valent molybdenum chem-... 

Although structurally related to the Mo hydroxylases, the active structure of the molybdenum containing CODH enzyme is unique among pyranopterin Mo enzymes in that it possesses a heterobimetallic Mo/Cu active site. " In the oxidized resting state, the Mo ion is in the Mo(vi) state while the Cu is reduced in the Cu(i) state. This is interesting since this leads to an oxidized active site that possesses metal centers that differ by five units in oxidation state and by ten d-electrons. However, only the Mo ion is believed to be redox active in the catalytic sequence. The Mo and Cu ions are covalently... 

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