Figure 4
Results of the third computational validation step for the proposed Cv-ATA inactivation model performed on the holo- dimer (PDB ID 4A6T, chains AB). Panels a and b show the MD snapshots (0 ns, 10 ns, 20 ns, 30 ns, 40 ns, 50 ns, 55 ns, 60 ns, 70 ns, progressive color palette blue-red-yellow) for the case of the coordinated methyl phosphonate in monomers A (panel a) and B (panel b). The coordinated phosphonate in the PGBC (panel a) rigidifies the conformation of the interfacial loop* inside the active site and hinders the rearrangement of the K288. The diffusion of the phosphonate away from the PGBC (panel b) makes the movement of the free K288 possible. Panels c and d show the MD snapshots (0 ns, 10 ns, 20 ns, 30 ns, 40 ns, 50 ns, 55 ns, 60 ns, 70 ns, progressive color palette blue-red-yellow) for the case of the phosphate-depleted PLP bound to the K288 via the Schiff base. The lack of coordinated phosphate, after inducing an initial reorganization of the interfacial loop*, is not observed to cause mayor conformational rearrangements in this region. During the course of the same simulation time, the K288, bound via the Schiff base to the PLP ring, rearranges towards the backward conformation. Significant directional rearrangements are indicated with discontinuous black arrows.
