Revertant mutation V48G alters conformational dynamics of highly drug resistant HIV protease PRS17.

ABSTRACT: Drug resistance is a serious problem for controlling the HIV/AIDS pandemic. Current antiviral drugs show several orders of magnitude worse inhibition of highly resistant clinical variant PRS17 of HIV-1 protease compared with wild-type protease. We have analyzed the effects of a common resistance mutation G48V in the flexible flaps of the protease by assessing the revertant PRS17_V48G for changes in enzyme kinetics, inhibition, structure, and dynamics. Both PRS17 and the revertant showed about 10-fold poorer catalytic efficiency than wild-type enzyme (0.55 and 0.39 μM^-1min^-1 compared to 6.3 μM^-1min^-1). Clinical inhibitors, amprenavir and darunavir, showed 2-fold and 8-fold better inhibition, respectively, of the revertant than of PRS17,

SUBMITTER: Burnaman SH 

PROVIDER: S-EPMC8435028 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature