NEW WAY TO TARGET HIV
STU BORMAN · Chemical & Engineering News · 2007
A NEWLY REVEALED drug-binding site on human immunodeficiency virus reverse transcriptase could lead to a new class of HIV medications. The site was observed in the X-ray crystal structure of a complex of HIV reverse transcriptase with the inhibitor dihydroxybenzoyl naphthyl hydrazone (DHBNH). The structure was determined and analyzed by Daniel M. Himmel and Stefan G. Sarafianos in structural biologist Eddy Arnold's group at the Center for Advanced Biotechnology & Medicine, Rutgers University, and their coworkers (ACS Chem. Biol 2006, 1, 702). Structures of drug complexes of HIV reverse transcriptase have been obtained before, but the site at which DHBNH binds was not observed in any of those. Reverse transcriptase has both RNase H (RNA-cleaving) and DNA polymerase (DNA-synthesizing) activity. Both activities are needed to reverse-transcribe HIV's RNA-based genomic material into DNA, an essential part of the virus's life cycle. DHBNH primarily inhibits the enzyme's RNase H activity. So Arnold and coworkers were surprised to ...