HIV-1 reverse transcriptase (RT) is an essential enzyme, targeting half of approved anti-AIDS drugs. While nucleoside RT inhibitors (NRTIs) are DNA chain terminators, the nucleotide-competing RT inhibitor (NcRTI) INDOPY-1 blocks dNTP binding to RT. Lack of structural information hindered INDOPY-1 improvement. Here we report the HIV-1 RT/DNA/INDOPY-1 crystal structure, revealing a unique mode of inhibitor binding at the polymerase active site without involving catalytic metal ions. The structure may enable new strategies for developing NcRTIs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737671 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.9b01289 | DOI Listing |
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