Structures of Reverse Transcriptase Pre- and Post-Excision Complexes Shed New Light on HIV-1 AZT Resistance

HIV-1 resistance to 3′-azido-2′,3′-deoxythymidine (AZT, zidovudine) results from mutations in reverse transcriptase that increase the ability of the enzyme to excise AZT-monophosphate after it has been incorporated. Crystal structures of complexes of wild type and mutant reverse transcriptase with double-stranded DNA with or without the excision product, AZT adenosine dinucleoside tetraphosphate (AZTppppA), have recently been reported [1]. The excision-enhancing mutations dramatically change the way the enzyme interacts with the excision product.