Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase.

Deoxynucleoside triphosphates (dNTPs) are the normal substrates for DNA synthesis catalyzed by polymerases such as HIV-1 reverse transcriptase (RT). However, substantial amounts of deoxynucleoside diphosphates (dNDPs) are also present in the cell. Use of dNDPs in HIV-1 DNA synthesis could have significant implications for the efficacy of nucleoside RT inhibitors such as AZT which are first line therapeutics for treatment of HIV infection. Our earlier work on HIV-1 reverse transcriptase (RT) suggested that the interaction between the gamma-phosphate of the incoming dNTP and RT residue K65 in the active site is not essential for dNTP insertion, implying that this polymerase may be able to insert dNDPs in addition to dNTPs.