transfer. Rates are proportion to decreasing substrate X-O bond strength and increasing substrate proton affinity. X-ray crystallography established that the overall tertiary structure of the enzyme remains constant through the reaction progression. However, several different experiments conducted on DMSOR of R. sphaeroides reported different results for the coordination activity of the four potential dithiolene ligands. While one x-ray crystallography investigation concluded equidistant coordination of all four Mo-S ligands in the oxidized form, which is supported by numerous x-ray absorption spectroscopy (XAS) studies, a different study characterized asymmetrical Mo-S distances. Both studies as well as electron paramagnetic resonance (EPR) studies have predicted that the Mo active site is highly flexible in terms of position and degree of potential ligand coordinations. The data that suggested two significantly asymmetric pyranopterin cofactors were used to propose a reaction mechanism. In the fully oxidized Mo VI form of the active site, the oxo-group and serine ligands were coordinated at 1.7 A distances from the Mo center. S1 and S2 of the P-pterin and S1 of the Q-pterin were locationed 2.4 A away from the Mo, and S2 of Q-pterin was located 3.1 A away. This pterin asymmetry may be the result of the trans-effect of the oxo-group weakening the S2-Mo bond, which is located directly opposite the oxo-group. In contrast, the structure of the fully reduced Mo IV form of the active site showed S1 and S2 P-pterin and S1 Q-pterin maintained full coordination, however the S2 of the Q-pterin shifted away from the metal center, indicating decreased coordination. This shift in ligand-Mo bond length is consistent with the proposed mechanism of direct oxygen transfer from the DMSO substrate to the Mo. A weaker dithiolene coordination in the reduced enzyme form could facilitate direct binding of the S=O. In the reduction of Mo and protonation of the oxo-group, it is proposed that a cytochrome electron source could bind to a depression above the active site and directly reduce the Mo center, or alternatively this cytochrome could bind to a well-solvated polypeptide loop in proximity to the Q-pterin, and Q-pterin could mediate this electron transfer. Cellular location and regulation In R. sphaeroides, DMSOR is a single-subunit, water-soluble protein that requires no additional cofactors beyond pterin. In E. coli, DMSOR is embedded within the membrane and has three unique subunits, one of which includes the characteristic pterin cofactor, another which contains four 4Fe:4S clusters, and a final