3I0S

crystal structure of HIV reverse transcriptase in complex with inhibitor 7

Summary for 3I0S

• Entry DOI: 10.2210/pdb3i0s/pdb
• Related: 3I0R
• Descriptor: Reverse transcriptase/ribonuclease H, p51 RT, S-{2-[(2-chloro-4-sulfamoylphenyl)amino]-2-oxoethyl} 6,8-dichloro-3,4-dihydroquinoline-1(2H)-carbothioate (3 entities in total)
• Functional Keywords: hiv-1 reverse transcriptase, non-nucleoside inhibition, nucleotidyltrasferase, aids, aspartyl protease, capsid maturation, capsid protein, cell membrane, cytoplasm, dna integration, dna recombination, dna-directed dna polymerase, endonuclease, host-virus interaction, hydrolase, lipoprotein, magnesium, membrane, metal-binding, multifunctional enzyme, myristate, nuclease, nucleotidyltransferase, nucleus, phosphoprotein, protease, ribosomal frameshifting, rna-binding, rna-directed dna polymerase, transferase, viral nucleoprotein, virion, zinc, zinc-finger
• Biological source: HIV-1 M:B_HXB2R (HIV-1); More
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P04585 P04585
• Total number of polymer chains: 2
• Total formula weight: 117135.56

Authors

Yan, Y.,Prasad, S. (deposition date: 2009-06-25, release date: 2009-08-25, Last modification date: 2023-09-06)

Primary citation

Su, D.S.,Lim, J.J.,Tinney, E.,Wan, B.L.,Young, M.B.,Anderson, K.D.,Rudd, D.,Munshi, V.,Bahnck, C.,Felock, P.J.,Lu, M.,Lai, M.T.,Touch, S.,Moyer, G.,Distefano, D.J.,Flynn, J.A.,Liang, Y.,Sanchez, R.,Prasad, S.,Yan, Y.,Perlow-Poehnelt, R.,Torrent, M.,Miller, M.,Vacca, J.P.,Williams, T.M.,Anthony, N.J.
Substituted tetrahydroquinolines as potent allosteric inhibitors of reverse transcriptase and its key mutants.
Bioorg.Med.Chem.Lett., 19:5119-5123, 2009

PubMed Abstract: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are key elements of multidrug regimens, called HAART (Highly Active Antiretroviral Therapy), that are used to treat HIV-1 infections. Elucidation of the structure-activity relationships of the thiocarbamate moiety of the previous published lead compound 2 provided a series of novel tetrahydroquinoline derivatives as potent inhibitors of HIV-1 RT with nanomolar intrinsic activity on the WT and key mutant enzymes and potent antiviral activity in infected cells. The SAR optimization, mutation profiles, preparation of compounds, and pharmacokinetic profile of compounds are described.

PubMed: 19631528
DOI: 10.1016/j.bmcl.2009.07.031

Experimental method

X-RAY DIFFRACTION (2.7 Å)