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Cited by 331

The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.

Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1.

Open access
Smerdon, S J, Jäger, J, Wang, J, Kohlstaedt, L A, Chirino, A J, Friedman, J M, Rice, P A, Steitz, T A·1994·Proceedings of the National Academy of Sciences

Abstract

The dipyridodiazepinone Nevirapine is a potent and highly specific inhibitor of the reverse transcriptase (RT) from human immunodeficiency virus type 1 (HIV-1). It is a member of an important class of nonnucleoside drugs that appear to share part or all of the same binding site on the enzyme but are susceptible to a variety of spontaneous drug-resistance mutations. The co-crystal-structure of HIV-1 RT and Nevirapine has been solved previously at 3.5-A resolution and now is partially refined against data extending to 2.9-A spacing. The drug is bound in a hydrophobic pocket and in contact with some 38 protein atoms from the p66 palm and thumb subdomains. Most, but not all, nonnucleoside drug-resistance mutations map to residues in close contact with Nevirapine. The major effects of these mutations are to introduce steric clashes with the drug molecule or to remove favorable protein-drug contacts. Additionally, four residues (Phe-227, Trp-229, Leu-234, and Tyr-319) in contact with Nevirapine have not been selected as sites of drug-resistance mutations, implying that there may be limitations on the number and types of resistance mutations that yield viable virus. Strategies of inhibitor design that target interactions with these conserved residues may yield drugs that are less vulnerable to escape mutations.

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Metadata

Authors
Smerdon, S. J., Jäger, J., Wang, J., Kohlstaedt, L. A., Chirino, A. J., Friedman, J. M., Rice, P. A., & Steitz, T. A.
Venue
Proceedings of the National Academy of Sciences
Published
1994-04-26
Volume
91
Issue
9
Pages
3911-3915
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2126644478
Cited by
331
References
27
FWCI
23.75
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1. https://app.cochat.ai/papers/10.1073/pnas.91.9.3911
The paper
Smerdon, S. J., Jäger, J., Wang, J., Kohlstaedt, L. A., Chirino, A. J., Friedman, J. M., Rice, P. A., & Steitz, T. A. (1994). Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.91.9.3911

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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