Allosteric regulation of HIV-1 reverse transcriptase by ATP for nucleotide selection.

ABSTRACT:

Background

Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a DNA polymerase that converts viral RNA genomes into proviral DNAs. How HIV-1 RT regulates nucleotide selectivity is a central issue for genetics and the nucleoside analog RT inhibitor (NRTI) resistance of HIV-1.

Methodology/principal findings

Here we show that an ATP molecule at physiological concentrations acts as an allosteric regulator of HIV-1 RT to decrease the K(m) value of the substrate, decrease the k(cat) value, and increase the K(i) value of NRTIs for RT. Computer-assisted structural analyses and mutagenesis studies suggested the positions of the ATP molecule and NRTI-resistance mutations during a catalytic reaction, which immediately predict possible influences on nucleotide inser

SUBMITTER: Yokoyama M 

PROVIDER: S-EPMC2810339 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature