Structural and functional similarities between HIV‐1 reverse transcriptase and the Escherichia coli RNA polymerase β′ subunit

Abstract

Four monoclonal antibodies (MAbs) recognizing HIV-1 reverse transcriptase (RT) were shown here to crossreact with the L LP P subunit of Escherichia coli RNA polymerase (RNAP). The anti-RT MAbs bind to a peptide comprising residues 294^305 of the RT amino acid sequence. Computer analyses revealed sequence similarity between this peptide and two regions of the RNAP L LP P subunit. MAb-binding studies using RT mutants suggested that the epitope is located to amino acids 652^663 of the L LP P sequence. One of the MAbs which inhibited the polymerase activity of RT also mediated a dose dependent inhibition of the RNAP activity. ß

A Search for Dual Action HIV-1 Reverse Transcriptase, Bacterial RNA Polymerase Inhibitors

“…Results revealed that the most potent of the studied compounds had IC 50 in the range of 3.3–18.5 µM against the HIV-1 wild-type, making them a good starting point for developing antiretroviral drugs. In turn, bacterial RNA polymerase (RNAP), a proven target for broad-spectrum antibacterial therapy [ 7 , 8 , 9 ], is structurally and functionally similar to reverse transcriptase (RT) [ 10 ]. Consequently, it is reasonable to suppose that our NNRTIs should also inhibit RNAP.…”

Macromolecule–semiconductor interfaces: From enzyme immobilization to photoelectrocatalytical applications

“…Although no conclusive information on the shape of the RT of AMV exists to date, it is possible to infer the tertiary structure from similarities with that of other retroviruses such as the RT of HIV-1, which is also a heterodimeric enzyme with two subunits [29]. Earlier STM observations of the HIV-1 RT have shown a rather circular molecule with an opening and a central depression [30].…”

“…Steric forces could also play a role. It is well known that RTs are conformationally flexible molecules with the ''fingers'' and ''thumb'' in an open conformation on binding a template primer [29]. As RTs approach the structured silicon surface such conformational changes may allow the enzyme to lock onto Si surface sites.…”

“…For constant current scanning tunneling experiments, HIV-1 RT was used because its structure is well-known [29] and high-resolution images were thought to allow insight into structure details that might be of medical importance. The HIV-1 RT structure is often referred to in analogy to the human right hand (see above) [29] and, therefore, with the in principle higher resolution of an STM experiment, the tertiary structure is expected to be imaged in high resolution.…”

“…The HIV-1 RT structure is often referred to in analogy to the human right hand (see above) [29] and, therefore, with the in principle higher resolution of an STM experiment, the tertiary structure is expected to be imaged in high resolution. An expected difficulty is the variation of the height of the molecule and its insulating character.…”