High resolution structures of HIV-1 RT from four RT-inhibitor complexes

Nat Struct Biol. 1995 Apr;2(4):293-302. doi: 10.1038/nsb0495-293.


We have determined the structures of four complexes of HIV-1 reverse transcriptase with non-nucleoside inhibitors, three fully refined at high resolution. The highest resolution structure is of the RT-nevirapine complex which has an R-factor of 0.186 and a root-mean-square bond length deviation of 0.015 A for all data to 2.2 A. The structures reveal a common mode of binding for these chemically diverse compounds. The common features of binding are largely hydrophobic interactions and arise from induced shape complementarity achieved by conformational rearrangement of the enzyme and conformational/configurational rearrangement of the compounds.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antiviral Agents / chemistry
  • Antiviral Agents / metabolism*
  • Binding Sites
  • Computer Graphics
  • Crystallography, X-Ray
  • Drug Design
  • HIV Reverse Transcriptase
  • HIV-1 / enzymology
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nevirapine
  • Point Mutation
  • Protein Conformation*
  • Protein Structure, Secondary
  • Pyridines / chemistry
  • Pyridines / metabolism*
  • RNA-Directed DNA Polymerase / chemistry*
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / chemistry
  • Reverse Transcriptase Inhibitors*


  • Antiviral Agents
  • Pyridines
  • Recombinant Proteins
  • Reverse Transcriptase Inhibitors
  • Nevirapine
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase