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

J Ren; R Esnouf; E Garman; D Somers; C Ross; I Kirby; J Keeling; G Darby; Y Jones; D Stuart

doi:10.1038/nsb0495-293

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.

Authors

J Ren¹, R Esnouf, E Garman, D Somers, C Ross, I Kirby, J Keeling, G Darby, Y Jones, D Stuart, et al.

Affiliation

¹ Laboratory of Molecular Biophysics, Oxford, UK.

PMID: 7540934
DOI: 10.1038/nsb0495-293

Abstract

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*

Substances

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