View source for 2opq

[[Image:2opq.jpg|left|200px]]

 {{Structure
|PDB= 2opq |SIZE=350|CAPTION= <scene name='initialview01'>2opq</scene>, resolution 2.80&Aring;
|SITE= 
|LIGAND= <scene name='pdbligand=CSW:CYSTEINE-S-DIOXIDE'>CSW</scene>, <scene name='pdbligand=HBQ:ISOPROPYL+(2S)-2-ETHYL-7-FLUORO-3-OXO-3,4-DIHYDROQUINOXALINE-1(2H)-CARBOXYLATE'>HBQ</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>
|ACTIVITY= <span class='plainlinks'>[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] </span>
|GENE= gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])
|DOMAIN=
|RELATEDENTRY=
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2opq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2opq OCA], [http://www.ebi.ac.uk/pdbsum/2opq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2opq RCSB]</span>
}}

'''Crystal Structure of L100I 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==
2OPQ 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=2OPQ 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:[http://www.ncbi.nlm.nih.gov/pubmed/17441703 17441703]
[[Category: Human immunodeficiency virus 1]]
[[Category: Protein complex]]
[[Category: RNA-directed DNA polymerase]]
[[Category: Chamberlain, P P.]]
[[Category: Chan, J H.]]
[[Category: Kleim, J.]]
[[Category: Nichols, C E.]]
[[Category: Ren, J.]]
[[Category: Short, S A.]]
[[Category: Stammers, D K.]]
[[Category: Weaver, K L.]]
[[Category: aid]]
[[Category: drug resistance]]
[[Category: gw420867x]]
[[Category: hiv-1 reverse transcriptase]]
[[Category: nnrti]]

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