1tkt
From Proteopedia
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==Overview== | ==Overview== | ||
| - | We have used a structure-based approach to design a novel series of | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: RNA-directed DNA polymerase]] | [[Category: RNA-directed DNA polymerase]] | ||
| - | [[Category: Hopkins, A | + | [[Category: Hopkins, A L.]] |
[[Category: Ren, J.]] | [[Category: Ren, J.]] | ||
| - | [[Category: Stammers, D | + | [[Category: Stammers, D K.]] |
| - | [[Category: Stuart, D | + | [[Category: Stuart, D I.]] |
[[Category: H12]] | [[Category: H12]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: nnrti]] | [[Category: nnrti]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:14:40 2008'' |
Revision as of 13:14, 21 February 2008
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CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH GW426318
Overview
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.
About this Structure
1TKT is a Protein complex structure of sequences from Human immunodeficiency virus 1 with , and as ligands. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Full crystallographic information is available from OCA.
Reference
Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 1., Hopkins AL, Ren J, Milton J, Hazen RJ, Chan JH, Stuart DI, Stammers DK, J Med Chem. 2004 Nov 18;47(24):5912-22. PMID:15537346
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