Pulsed EPR characterization of HIV-1 protease conformational sampling and inhibitor-induced population shifts.

ABSTRACT: The conformational landscape of HIV-1 protease (PR) can be experimentally characterized by pulsed-EPR double electron-electron resonance (DEER). For this characterization, nitroxide spin labels are attached to an engineered cysteine residue in the flap region of HIV-1 PR. DEER distance measurements from spin-labels contained within each flap of the homodimer provide a detailed description of the conformational sampling of apo-enzyme as well as induced conformational shifts as a function of inhibitor binding. The distance distribution profiles are further interpreted in terms of a conformational ensemble scheme that consists of four unique states termed "curled/tucked", "closed", "semi-open" and "wide-open" conformations. Reported here are the DEER results for a drug-resistant variant clini

SUBMITTER: Liu Z 

PROVIDER: S-EPMC4758878 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature