The active site of the mononuclear molybdenum enzyme xanthine oxidase has an LMoOS(OH) center that catalyzes the hydroxylation of substrate (L representing an enedithiolate ligand contributed by a pterin cofactor in the enzyme). Reaction of the enzyme with cyanide results in the replacement of the Mo=S group with a second Mo=O group, which results in loss of enzyme activity. To understand the basis for this loss of activity, we have computationally examined the interaction of a model for the LMoO2(OH) as well the LMoOTe(OH) congener of the enzyme with formamide (a substrate for the enzyme). Our electronic structure calculations for the oxo congener indicate a reduced electron density on the hydrogen being transferred from substrate in the course of the reaction, a shorter O-H bond in the transition state, and a longer nascent O-C bond of product, factors which combine to account for the loss of reactivity in the LMoO2(OH) species. Interestingly, our calculations indicate that the Te congener is characterized by an increased electron density on the hydrogen species being transferred, a longer Te-H bond in the transition state, and a shorter O-C nascent bond in the product and suggest that a Te congener of xanthine oxidase, were it to be prepared experimentally, should exhibit catalytic activity.