A broader active site in CoA disulfide reductase accommodates larger substrates and reveals evidence of subunit asymmetry.

Within the family of pyridine nucleotide disulfide oxidoreductase (PNDOR), enzymes are a group of single-cysteine containing FAD-dependent reductases that utilize a tightly bound coenzyme A to assist in the NAD(P)H-dependent reduction of di-, per-, and polysulfide substrates in bacteria and archaea. For many of these homodimeric enzymes, it has proved difficult to determine the substrate specificity and metabolic function based on sequence and genome analysis alone. Coenzyme A-disulfide reductase (CoADR) isolated from (CoADR) reduces Co-A per- and polysulfides, but, unlike other highly homologous members of this group, is a poor CoA disulfide reductase.