|
|
| Line 1: |
Line 1: |
| [[Image:1fko.gif|left|200px]] | | {{Seed}} |
| | [[Image:1fko.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_1fko| PDB=1fko | SCENE= }} | | {{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)=== |
|
| |
|
|
| |
|
| ==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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11080630}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11080630 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_11080630}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 36: |
Line 40: |
| [[Category: Hiv-1 reverse transcriptase]] | | [[Category: Hiv-1 reverse transcriptase]] |
| [[Category: Non-nucleoside inhibitor]] | | [[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 Tue Jul 1 03:24:35 2008'' |
