Symphoria: the success of modeling the active site function of oxo-molybdoenzymes

The success of modeling the active site function of oxomolybdoenzymes have been claimed generally on the basis of reactivity of the synthetic analogues towards PPh(3) or DMSO (dimethyl sulfoxide). Here it has been shown that the success of modeling the active site function of these enzymes may not be determined by the ability of a model to undergo oxotransfer with PPh(3) or DMSO (except for the modeling of DMSO reductase) and one should adhere to the criteria accepted by the bioinorganic community. A critical evaluation of two of those criteria which requires a synthetic analogue (a) should react with the enzyme substrate (b) should follow the same rate law as does the enzyme, has been presented in this paper. We have shown that the fulfillment of criterion (b) and the inhibition phenomena to that effect both are dictated by symphoria (from sympherin in Greek: the bringing together of reactants into the proper spatial relationship) on the basis of kinetic studies of the reactivity of enzyme substrate the HSO(3)(-) and its analogues (anions of oxyacids of phosphorous) towards a functional model sulfite oxidase Bu(4)N](2)Mo(VI)O(2)(mnt)(2)] (mnt(2-)=1,2-dicyanoethylenedithiolate) but with the caveat that the mechanistic inference drawn from such studies may not be the same as in the case of native enzyme. In view of this ambiguity it has been pointed out that the fulfillment of this criterion is not a definitive conclusion towards our understanding of the structure-function relationship of an enzyme and, therefore, the criterion of a 'structural analogue' and 'functional analogue' have been revised subject to an amendment of criterion (a) to include substrate analogues. It has also been shown for the first time on the basis of kinetic studies that the effect of medium can lead to substrate - inhibitor type dualism and hence the effect of medium is also a factor that can play a key role for the success of modeling the active site function of an enzyme. Here we also provide the details of the inhibition mechanisms proposed in our earlier report with an indirect proof to that effect.