[3] Trimethylamine N-oxide reductase has the EC number 1.7.2.3, and these components refer to the following enzyme classifications: TMAO is an organic osmolyte that has the useful biological function of protecting proteins against denaturing stresses such as high concentration of urea.
[5] Various bacteria grow anaerobically using TMAO as an alternative electron transport chain, allowing for growth on non-fermentable carbon sources such as glycerol.
[5] TMAO reductases have been studied in several organisms, and a common conserved feature is the presence of a molybdenum cofactor in all the known terminal enzymes.
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.
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.
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.