1fkp: Difference between revisions
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|PDB= 1fkp |SIZE=350|CAPTION= <scene name='initialview01'>1fkp</scene>, resolution 2.9Å | |PDB= 1fkp |SIZE=350|CAPTION= <scene name='initialview01'>1fkp</scene>, resolution 2.9Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=NVP:11-CYCLOPROPYL-5,11-DIHYDRO-4-METHYL-6H-DIPYRIDO[3,2-B | |LIGAND= <scene name='pdbligand=NVP:11-CYCLOPROPYL-5,11-DIHYDRO-4-METHYL-6H-DIPYRIDO[3,2-B:2',3'-E][1,4]DIAZEPIN-6-ONE'>NVP</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] | |ACTIVITY= [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] | ||
|GENE= | |GENE= | ||
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[[Category: non-nucleoside inhibitor]] | [[Category: non-nucleoside inhibitor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 11:48:02 2008'' | ||
Revision as of 12:48, 23 March 2008
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| , resolution 2.9Å | |||||||
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| Activity: | RNA-directed DNA polymerase, with EC number 2.7.7.49 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF NNRTI RESISTANT K103N MUTANT HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH NEVIRAPINE
OverviewOverview
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 StructureAbout this Structure
1FKP is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
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
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