text: In E. coli, it has been shown that an inducible, periplasmic TMAO reductase is responsible for almost all TMAO reduction (with the rest being DMSO reduction). While no structural analysis of this E. coli enzyme has been reported, TMAO reductase from Shewanella massilia has been isolated and characterized at a resolution of 2.5 Å.
  TMAO reductases have been studied in several organisms, and a common feature is the presence of a molybdenum cofactor in all the known terminal enzymes. The common form of the molybdopterin molecule is a tricyclic ring system comprising a pterin group fused to a pyran ring. The role of this pyran ring could be a way of controlling the oxidation state of the molybdenum cofactor and/or facilitating proton diffusion. Furthermore, the arrangement of aromatic residues in the funnel-like entrance leading to the active center is closely related to that of DMSO reductase structures. A hydrophobic pocket, formed by two tryptophan and two tyrosine residues, is also present in the TMAO reductase and contains highly conserved residues.
  When comparing TMAO reductase of S. massilia to DMSO reductase from R. Sphaeroides and R. capsulatus, the overall structure is strikingly similar. However, one major difference in TMAO reductase is a missing tyrosine (Tyr114), in DMSO reductase of R. capsulatus. It is replaced by a threonine (Thr116) in the TMAO reductase, and the backbone stretch around this residue, from residue 100 to 116, is not identical to that in the DMSO reductases. A direct consequence of the missing residue is a wider accessible space, adjacent to the molybdenum active center, which potentially exists to accommodates the somewhat bulkier trimethylamine-oxide molecules more easily than the dimethylsulfoxide molecules. This different demonstrates how an enzyme's form is almost always directly tied to its function.
  However, recent discrepancies have risen regarding the structure of the TMAO reductase active site. The proposed active site contains several anomalous bond lengths; one Mo-O bond length is too short for a Mo-O single-bond coordination, and the four Mo-S bond lengths are all considerably longer than expected. Moreover, the proposed molybdenum coordination of the active site is extremely crowded, with the distances between several supposedly nonbonding atoms being significantly shorter than the sum of their van der Waals radii and some bond angles being unreasonably small. Now, it is being hypothesized that this overcrowding is due to the cocrystallization of multiple forms of the enzyme.