Non-nucleoside Reverse Transcriptase Inhibitors Inhibit Reverse Transcriptase through a Mutually Exclusive Interaction with Divalent Cation-dNTP Complexes.

ABSTRACT: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are considered noncompetitive inhibitors that structurally alter reverse transcriptase (RT) and dramatically decrease catalysis. In this report, biochemical analysis with various divalent cations was used to demonstrate that NNRTIs and divalent cation-dNTP complexes are mutually exclusive, inhibiting each other's binding to RT/primer/template (RT-P/T) complexes. The binding of catalytically competent divalent cation-dNTP complexes to RT-P/T was measured with Mg²⁺, Mn²⁺, Zn²⁺, Co²⁺, and Ni²⁺ using Ca²⁺, a noncatalytic cation, for displacement. Binding strength order was Mn²⁺ ≈ Zn²⁺ ≫ Co²⁺ > Mg²⁺ ≈ Ni²⁺. Consistent w

SUBMITTER: DeStefano JJ 

PROVIDER: S-EPMC6629025 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature