HIV-1 RT enhances the activity of a tethered dimer of HIV-1 proteinase

Abstract

HIV-1 reverse transcriptase (RT) can specifically enhance HIV-1 proteinase activity in vitro and in eukaryotic cells (1). To determine if the effect of RT on proteinase activity was due to changes in the equilibrium dimerization constant of the proteinase or the stability of the proteinase dimer, we studied the effect of RT on a genetically engineered covalent dimer (tethered dimer) of the proteinase. RT was found to increase the activity of the tethered dimer independent of pH and ionic strength. The effect of RT on the kinetic constants (Km and kcat) of the wild type HIV-1 proteinase and its tethered dimer were also determined. These results show that RT can increase the enzymatic catalytic efficiency and substrate affinity of the proteinase, by a mechanism independent of promoting dimer formation