The results of a modeling study indicated that reduced susceptibility to cephems such as cefixime and ceftriaxone is due to a conformational alteration of the beta-lactam-binding pocket caused by an A501 mutation in non-mosaic strains [ 13].
The extended conformation protrudes into the substrate binding pocket, causing steric clashes with bound d-Thy and interfering with substrate binding as observed in our experiments.
Detailed analysis of the dissociation processes of inhibitors from the PR binding pocket showed that the different binding strength was caused by the difference in the stability of H-bond networks in the bound complexes.
Furthermore, in silico mutagenesis studies indicate that the K321T and A65 V mutations, which directly form the predicted binding pocket, would cause significant losses (Δaffinity = +1.41 and 0.95, respectively) in the affinity of S20 for the pocket.
Pocket closure of the Leu91-binding site was caused by rearrangements in α1, α2 and β2, which moved towards the pocket.
Probably, change in its conformation within the binding pocket of LPKC was caused by loss of H-bonds between certain parts of withaferin A and protein.
Significant effects of minor structural changes in the binding pocket of the enzyme, caused by the substitutions S119A, I369L, I369F, A370L, and A370V, were observed, demonstrating a profound sensitivity of both the enzyme substrate binding interactions and the catalytic efficiency of CYP3A4.
It is hypothesized that net negative or neutral charges in binding pocket 4 cause poor binding of the DRB1 molecule to M. leprae antigens.
Therefore ETVr substitutions at T184 or S202 can cause resistance to ETV through steric repositioning of the YMDD loop and shrinking the ETV-TP binding pocket, or by disrupting the H-bonding network that stabilized the active site conformation.
They are located in and near the binding pocket facilitated by crystal packing effects.
