HIV integrase inhibitor, Elvitegravir, impairs RAG functions and inhibits V(D)J recombination.

ABSTRACT: Integrase inhibitors are a class of antiretroviral drugs used for the treatment of AIDS that target HIV integrase, an enzyme responsible for integration of viral cDNA into host genome. RAG1, a critical enzyme involved in V(D)J recombination exhibits structural similarity to HIV integrase. We find that two integrase inhibitors, Raltegravir and Elvitegravir, interfered with the physiological functions of RAGs such as binding, cleavage and hairpin formation at the recombination signal sequence (RSS), though the effect of Raltegravir was limited. Circular dichroism studies demonstrated a distinct change in the secondary structure of RAG1 central domain (RAG1 shares DDE motif amino acids with integrases), and when incubated with Elvitegravir, an equilibrium dissociation constant (K_d)

SUBMITTER: Nishana M 

PROVIDER: S-EPMC5520896 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature