Substrate orientation and the origin of catalytic power in xanthine oxidoreductase

Abstract

With the chemical course of the reaction catalyzed by the molybdenum-containing hydroxylase xanthine oxidoreductase now relatively well-understood, efforts in the field have now turned to understanding the catalytic power of the enzyme in the context of its structure. The present minireview is an account of recent efforts, from the authors’ laboratory and elsewhere, towards understanding the role of active site amino acid residues in accelerating reaction rate. On the basis of recent site-directed mutagenesis work, in conjunction with protein X-ray crystallography, it is now possible to attribute the specific extent to which each contributes to transition state stabilization and the means by which this occurs.