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,