Effects of the M45I, M45R, M45V, A20S, A20SV, and A50V mutations on thePlasmodium5 P1 binding pocket. To facilitate comparison, the 5 P1 binding pocket of the wild-type proteasome (boxed in green) is shown in the same orientation as each of the selection mutants (cyan boxes). For all mutations, the proteasome models indicate that resistance to the selection compounds is primarily mediated by steric constraints that limit their access to the P1 binding site. Examples of sensitization (yellow boxes) and cross resistance (magenta boxes) are also shown. Protein models are represented as Van der Waals surfaces colored by electrostatic potential, overlaid with inhibitors.
