Structures of reverse transcriptase pre- and post-excision complexes shed new light on HIV-1 AZT resistance

Viruses. 2011 Jan;3(1):20-25. doi: 10.3390/v3010020. Epub 2011 Jan 18.

Abstract

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. The excision-enhancing mutations dramatically change the way the enzyme interacts with the excision product.

Keywords: AZT resistance; AZTppppA; HIV; nucleotide excision; reverse transcriptase.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites / drug effects
  • Crystallography, X-Ray
  • Drug Design
  • Drug Resistance, Viral / genetics*
  • HIV Reverse Transcriptase* / chemistry
  • HIV Reverse Transcriptase* / genetics
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Models, Molecular
  • Mutation / genetics*
  • Protein Conformation
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Zidovudine / analogs & derivatives
  • Zidovudine / metabolism
  • Zidovudine / pharmacology*

Substances

  • Reverse Transcriptase Inhibitors
  • Zidovudine
  • HIV Reverse Transcriptase