EVCoupling analysis also revealed another FPEC pair involving residues (D120/K316) near the structural siroheme moiety (in A. fulgidus ) (bold in Table 2). This pair was identified as an FPEC pair when compared against a contact map of the D. vulgaris DsrAB X-ray crystal structure. However, when highlighted on the structure of A. fulgidus DsrAB, the residues are in contact. Hence it is a true contact for some members of the protein family, and a false predicted contact for others. Aligning the three structures of DsrAB from A. fulgidus , D. vulgaris, and the model of MV2-Eury (Figure 8) reveals an antiparallel β-hairpin/loop insert in the A. fulgidus DsrB subunit (Figure 8, light pink) which brings aspartate 120B within 7.4 Å of lysine 316B and also makes contact with the end of a helix in the DsrA subunit. This insert includes a tryptophan residue (in CPK color) that blocks access to the structural heme in the A. fulgidus structure (see also Figure 3). The MV2-Eury and D. vulgaris DsrB subunits (Figure 8, cyan, deep teal) lack this extension. The phenylalanine residue in these sequences, that corresponds to the aspartate in the FPEC pair residue D120B/K316B in A. fulgidus, is far (~27 Å) from its co-evolving partner residue (Figure 8, red, raspberry sticks on the right side), thus providing a false positive signal. Interestingly, this insert in the DsrB subunit of A. fulgidus (Figure 3, pink) is absent from all other DsrB sequences (Fig. 9), posing the question of why the co-evolutionary coupling probability was high (99%) for this pair.