Targeting the Structural Maturation Pathway of HIV-1 Reverse Transcriptase.

ABSTRACT: Formation of active HIV-1 reverse transcriptase (RT) proceeds via a structural maturation process that involves subdomain rearrangements and formation of an asymmetric p66/p66' homodimer. These studies were undertaken to evaluate whether the information about this maturation process can be used to identify small molecule ligands that retard or interfere with the steps involved. We utilized the isolated polymerase domain, p51, rather than p66, since the initial subdomain rearrangements are largely limited to this domain. Target sites at subdomain interfaces were identified and computational analysis used to obtain an initial set of ligands for screening. Chromatographic evaluations of the p51 homodimer/monomer ratio support the feasibility of this approach. Ligands that bind near the interf

SUBMITTER: Kirby TW 

PROVIDER: S-EPMC10669680 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature