High resolution structures of HIV-1 RT from four RT–inhibitor complexes
- 1 April 1995
- journal article
- research article
- Published by Springer Nature in Nature Structural & Molecular Biology
- Vol. 2 (4) , 293-302
- https://doi.org/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.Keywords
This publication has 39 references indexed in Scilit:
- Potent and highly selective human immunodeficiency virus type 1 (HIV-1) inhibition by a series of alpha-anilinophenylacetamide derivatives targeted at HIV-1 reverse transcriptase.Proceedings of the National Academy of Sciences, 1993
- Crystal Structure at 3.5 Å Resolution of HIV-1 Reverse Transcriptase Complexed with an InhibitorScience, 1992
- Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture.Proceedings of the National Academy of Sciences, 1991
- An antiviral target on reverse transcriptase of human immunodeficiency virus type 1 revealed by tetrahydroimidazo-[4,5,1-jk] [1,4]benzodiazepin-2 (1H)-one and -thione derivatives.Proceedings of the National Academy of Sciences, 1991
- A novel, dipyridodiazepinone inhibitor of HIV-1 reverse transcriptase acts through a nonsubstrate binding siteBiochemistry, 1991
- Inhibition of HIV-1 Replication by a Nonnucleoside Reverse Transcriptase InhibitorScience, 1990
- Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivativesNature, 1990
- Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6-substituted acyclouridine derivativeBiochemical and Biophysical Research Communications, 1989
- Multiple Mutations in HIV-1 Reverse Transcriptase Confer High-Level Resistance to Zidovudine (AZT)Science, 1989
- Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS)Science, 1983