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.

Type

Journal article

Journal

Nat Struct Biol

Publication Date

04/1995

Volume

2

Pages

293 - 302

Keywords

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