Abstract
Human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) has a unique tight binding to dNTP substrates. Structural modeling of Ala-114 of HIV-1 RT suggests that longer side chains at this residue can reduce the space normally occupied by the sugar moiety of an incoming dNTP. Indeed, mutations at Ala-114 decrease the ability of RT to synthesize DNA at low dNTP concentrations and reduce the dNTP-binding affinity (K d) of RT. However, the K d values of WT and A114C RT remained equivalent with an acyclic dNTP substrate. Finally, mutant A114 RT HIV-1 vectors displayed a greatly reduced transduction in nondividing human lung fibroblasts (HLFs), while WT HIV-1 vector efficiently transduced both dividing and nondividing HLFs. Together these data support that the A114 residue of HIV-1 RT plays a key mechanistic role in the dNTP binding of HIV-1 RT and the unique viral infectivity of target cell types with low dNTP pools.
Original language | English (US) |
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Pages (from-to) | 393-401 |
Number of pages | 9 |
Journal | Virology |
Volume | 422 |
Issue number | 2 |
DOIs | |
State | Published - Jan 20 2012 |
Externally published | Yes |
Keywords
- Cellular dNTP pools
- DNTP binding affinity
- HIV-1
- Reverse transcriptase
- Steady and presteady kinetics
ASJC Scopus subject areas
- Virology