1TKT

CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH GW426318

Summary for 1TKT

• Entry DOI: 10.2210/pdb1tkt/pdb
• Descriptor: Pol polyproteins [Reverse transcriptase], Chain A, Pol polyproteins [Reverse transcriptase], Chain B, PHOSPHATE ION, ... (6 entities in total)
• Functional Keywords: hiv-1 reverse transcriptase, aids, nnrti, gw426318, drug design, transferase
• Biological source: Human immunodeficiency virus 1; More
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585 P04585
• Total number of polymer chains: 2
• Total formula weight: 116623.04

Authors

Hopkins, A.L.,Ren, J.,Stuart, D.I.,Stammers, D.K. (deposition date: 2004-06-09, release date: 2004-12-07, Last modification date: 2024-10-30)

Primary citation

Hopkins, A.L.,Ren, J.,Milton, J.,Hazen, R.J.,Chan, J.H.,Stuart, D.I.,Stammers, D.K.
Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 1.
J.Med.Chem., 47:5912-5922, 2004

PubMed Abstract: We have used a structure-based approach to design a novel series of non-nucleoside inhibitors of HIV-1 RT (NNRTIs). Detailed analysis of a wide range of crystal structures of HIV-1 RT-NNRTI complexes together with data on drug resistance mutations has identified factors important for tight binding of inhibitors and resilience to mutations. Using this approach we have designed and synthesized a novel series of quinolone NNRTIs. Crystal structure analysis of four of these compounds in complexes with HIV-1 RT confirms the predicted binding modes. Members of this quinolone series retain high activity against the important resistance mutations in RT at Tyr181Cys and Leu100Ile.

PubMed: 15537346
DOI: 10.1021/jm040071z

Experimental method

X-RAY DIFFRACTION (2.6 Å)