During the past four years, a substantial amount of structural information has been accumulated on the molybdoenzyme dimethyl sulfoxide (DMSO) reductase from purple bacteria. This enzyme contains a mononuclear Mo coordinated by two molybdopterin guanine dinucleotides as its single cofactor. Crystallographic studies on the enzyme from Rhodobacter sphaeroides and Rhodobacter capsulatus revealed substantial differences in the Mo coordination environment in the oxidized Mo(VI) state, despite a close structural similarity in the overall fold of the protein. The crystal structure of DMSO reductase from R. sphaeroides identified a Mo environment with a mono-oxo ligation and an asymmetric coordination by the two molybdopterins, with three short and one very long Mo−S bond. In contrast, two independent crystallographic studies of the enzyme from R. capsulatus revealed two additional Mo coordination environments:  a pentacoordinated dioxo metal ligation sphere in which one molybdopterin is completely dissociated from the Mo and a heptacoordinated environment with symmetrical metal coordination by both molybdopterins and two oxo ligands. In all three structures the side chain of a serine was a ligand to the Mo. Adding to the controversy, EXAFS studies on the R. sphaeroides enzyme suggested a hexacoordinated active site geometry, whereas the same technique indicated seven ligands for the R. capsulatus enzyme. The 1.3 Å resolution crystal structure of oxidized DMSOR from R. sphaeroides presented here reveals plasticity at the active site. The Mo is discretely disordered and exists in a hexacoordinated and a pentacoordinated ligation sphere. The hexacoordinated model reconciles the existing differences in active site coordination of R. sphaeroides DMSO reductase as studied by crystallographic and EXAFS techniques. In addition, the pentacoordinated structure closely resembles one of the reported R. capsulatus crystal structures. In retrospect, the active site geometry in the previously reported 2.2 Å crystal structure of R. sphaeroides DMSO reductase appears to represent an average of the two conformations described here. Thus, structural flexibility at the active site appears to give rise to the observed differences in the Mo coordination environment.

Dimethylsulfoxide reductase is a molybdenum cofactor‐containing enzyme, which catalyzes the two‐electron reduction of dimethylsulfoxide to dimethylsulfide. The enzyme consists of a single polypeptide chain of 780 amino acids and contains no other cofactor besides the molybdenum cofactor. The overall fold of the enzyme is structurally organized into four domains, which are grouped around the cofactor. The molybdenum cofactor consists of two molybdopterin guanine dinucleotides, which are symmetrically ligating the molybdenum with their dithiolene groups. In the oxidized Mo(VI) form of the enzyme, an oxo group and a serine side chain complete the coordination sphere. The oxo group is the catalytically labile oxygen, which is replaced by an aquo or, possibly, a hydroxo ligand in the reduced Mo(IV) state.