Identification of a Potential Allosteric Pathway in DsrAB
Two sets of high co-variance probability (>80%) FPEC pairs (Table 1, bold) were observed using the A. fulgidus DsrA and DsrB subunits as queries in the EVCoupling calculations. Table 1 lists the homologous residues in the DsrB (or DsrA) subunits for these FPEC pairs for the three DsrAB structures in Figure 2, along with the FPEC distance and the coupling probability. Given the large distances between the putative co-varying residues in the monomers, and hence the false positive nature of the pair, the Res1A1-Res2A1 and Res1B1-Res2B1 co-variances are eliminated, leaving six remaining possible pairs of co-varying residues. Highlighting the four residues from
the two A and two B subunits (eight residues in all) on the DsrAB structure (Figure 5A-C), it is particularly striking that three out of four of the possible implicated residues for each of the two sets of monomer FPEC pairs describe a path from the functional heme in one heterodimer to that
in the other heterodimer. We refer to this pathway as the “heme road”. The fourth possible co-varying residue (Table 1) from each heterodimer, N222A1/2, is in a homologous structural position as N180B in the structural alignment of the A and B subunits (Figure S4), but in the heterotetramer N222A1/2 interacts with the “lower” inactive, structural siroheme at a distance of 20.5 Å from the nearest of the three other possible co-varying residues, whereas the homologous N180 of the DsrB subunit is proximal to the “upper” active siroheme and one of the nearby Fe-S centers,