2opr
From Proteopedia
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| - | [[Image:2opr.jpg|left|200px]] | + | [[Image:2opr.jpg|left|200px]] |
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| - | '''Crystal Structure of K101E Mutant HIV-1 Reverse Transcriptase in Complex with GW420867X.''' | + | {{Structure |
| + | |PDB= 2opr |SIZE=350|CAPTION= <scene name='initialview01'>2opr</scene>, resolution 2.90Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=HBQ:ISOPROPYL (2S)-2-ETHYL-7-FLUORO-3-OXO-3,4-DIHYDROQUINOXALINE-1(2H)-CARBOXYLATE'>HBQ</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] | ||
| + | |GENE= gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal Structure of K101E Mutant HIV-1 Reverse Transcriptase in Complex with GW420867X.''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2OPR is a [ | + | 2OPR is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OPR OCA]. |
==Reference== | ==Reference== | ||
| - | Relationship of potency and resilience to drug resistant mutations for GW420867X revealed by crystal structures of inhibitor complexes for wild-type, Leu100Ile, Lys101Glu, and Tyr188Cys mutant HIV-1 reverse transcriptases., Ren J, Nichols CE, Chamberlain PP, Weaver KL, Short SA, Chan JH, Kleim JP, Stammers DK, J Med Chem. 2007 May 17;50(10):2301-9. Epub 2007 Apr 19. PMID:[http:// | + | Relationship of potency and resilience to drug resistant mutations for GW420867X revealed by crystal structures of inhibitor complexes for wild-type, Leu100Ile, Lys101Glu, and Tyr188Cys mutant HIV-1 reverse transcriptases., Ren J, Nichols CE, Chamberlain PP, Weaver KL, Short SA, Chan JH, Kleim JP, Stammers DK, J Med Chem. 2007 May 17;50(10):2301-9. Epub 2007 Apr 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17441703 17441703] |
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: Weaver, K L.]] | [[Category: Weaver, K L.]] | ||
[[Category: HBQ]] | [[Category: HBQ]] | ||
| - | [[Category: | + | [[Category: aid]] |
[[Category: drug resistance]] | [[Category: drug resistance]] | ||
[[Category: gw420867x]] | [[Category: gw420867x]] | ||
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[[Category: nnrti]] | [[Category: nnrti]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:02:54 2008'' |
Revision as of 16:02, 20 March 2008
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| , resolution 2.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | gag-pol (Human immunodeficiency virus 1) | ||||||
| Activity: | RNA-directed DNA polymerase, with EC number 2.7.7.49 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of K101E Mutant HIV-1 Reverse Transcriptase in Complex with GW420867X.
Overview
The selection of drug resistant viruses is a major problem in efforts to combat HIV and AIDS, hence, new compounds are required. We report crystal structures of wild-type and mutant HIV-1 RT with bound non-nucleoside (NNRTI) GW420867X, aimed at investigating the basis for its high potency and improved drug resistance profile compared to the first-generation drug nevirapine. GW420867X occupies a smaller volume than many NNRTIs, yet accesses key regions of the binding pocket. GW420867X has few contacts with Tyr188, hence, explaining the small effect of mutating this residue on inhibitor-binding potency. In a mutated NNRTI pocket, GW420867X either remains in a similar position compared to wild-type (RT(Leu100Ile) and RT(Tyr188Cys)) or rearranges within the pocket (RT(Lys101Glu)). For RT(Leu100Ile), GW420867X does not shift position, in spite of forming different side-chain contacts. The small bulk of GW420867X allows adaptation to a mutated NNRTI binding site by repositioning or readjustment of side-chain contacts with only small reductions in binding affinity.
About this Structure
2OPR is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
Relationship of potency and resilience to drug resistant mutations for GW420867X revealed by crystal structures of inhibitor complexes for wild-type, Leu100Ile, Lys101Glu, and Tyr188Cys mutant HIV-1 reverse transcriptases., Ren J, Nichols CE, Chamberlain PP, Weaver KL, Short SA, Chan JH, Kleim JP, Stammers DK, J Med Chem. 2007 May 17;50(10):2301-9. Epub 2007 Apr 19. PMID:17441703
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