1fko
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1fko.gif|left|200px]] | [[Image:1fko.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1fko", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1fko| PDB=1fko | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''CRYSTAL STRUCTURE OF NNRTI RESISTANT K103N MUTANT HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH DMP-266(EFAVIRENZ)''' | '''CRYSTAL STRUCTURE OF NNRTI RESISTANT K103N MUTANT HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH DMP-266(EFAVIRENZ)''' | ||
| Line 32: | Line 29: | ||
[[Category: Stuart, D I.]] | [[Category: Stuart, D I.]] | ||
[[Category: Weaver, K L.]] | [[Category: Weaver, K L.]] | ||
| - | [[Category: | + | [[Category: Aid]] |
| - | [[Category: | + | [[Category: Dmp-266]] |
| - | [[Category: | + | [[Category: Drug design]] |
| - | [[Category: | + | [[Category: Drug resistance mutation]] |
| - | [[Category: | + | [[Category: Efavirenz]] |
| - | [[Category: | + | [[Category: Hiv-1 reverse transcriptase]] |
| - | [[Category: | + | [[Category: Non-nucleoside inhibitor]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:26:21 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 13:26, 2 May 2008
CRYSTAL STRUCTURE OF NNRTI RESISTANT K103N MUTANT HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH DMP-266(EFAVIRENZ)
Overview
BACKGROUND: Efavirenz is a second-generation non-nucleoside inhibitor of HIV-1 reverse transcriptase (RT) that has recently been approved for use against HIV-1 infection. Compared with first-generation drugs such as nevirapine, efavirenz shows greater resilience to drug resistance mutations within HIV-1 RT. In order to understand the basis for this resilience at the molecular level and to help the design of further-improved anti-AIDS drugs, we have determined crystal structures of efavirenz and nevirapine with wild-type RT and the clinically important K103N mutant. RESULTS: The relatively compact efavirenz molecule binds, as expected, within the non-nucleoside inhibitor binding pocket of RT. There are significant rearrangements of the drug binding site within the mutant RT compared with the wild-type enzyme. These changes, which lead to the repositioning of the inhibitor, are not seen in the interaction with the first-generation drug nevirapine. CONCLUSIONS: The repositioning of efavirenz within the drug binding pocket of the mutant RT, together with conformational rearrangements in the protein, could represent a general mechanism whereby certain second-generation non-nucleoside inhibitors are able to reduce the effect of drug-resistance mutations on binding potency.
About this Structure
1FKO is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
Structural basis for the resilience of efavirenz (DMP-266) to drug resistance mutations in HIV-1 reverse transcriptase., Ren J, Milton J, Weaver KL, Short SA, Stuart DI, Stammers DK, Structure. 2000 Oct 15;8(10):1089-94. PMID:11080630 Page seeded by OCA on Fri May 2 16:26:21 2008
Categories: Human immunodeficiency virus 1 | Protein complex | RNA-directed DNA polymerase | Milton, J. | Ren, J. | Short, S A. | Stammers, D K. | Stuart, D I. | Weaver, K L. | Aid | Dmp-266 | Drug design | Drug resistance mutation | Efavirenz | Hiv-1 reverse transcriptase | Non-nucleoside inhibitor
