To assess the role of these 4 active-site proximal residues -T310, H236, S14 and H314 -we examined their homology in related enzymes in the Type-I pyridine nucleotide-disulfide oxidoreductase family. An analysis of 13 GSHRs, GRLMR, Mercuric Reductase, and Tellurite reductase shows that the disulfide is universally conserved, as expected for a catalytic active site. Similarly, S14 is conserved in all analyzed enzymes except for mercuric reductase where it is Alanine. T310 is conserved in all considered enzymes except for mercuric reductase and tellurite reductase, where it is V and K respectively. The highly conserved nature of S14 and T310 implicates these residues in catalysis.