View source for 2ops

[[Image:2ops.gif|left|200px]]<br />
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'''Crystal Structure of Y188C Mutant HIV-1 Reverse Transcriptase in Complex with GW420867X.'''<br />

==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==
2OPS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with PO4 and HBQ as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2OPS 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):2301-2309. Epub 2007 Apr 19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=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: HBQ]]
[[Category: PO4]]
[[Category: aids]]
[[Category: drug resistance]]
[[Category: gw420867x]]
[[Category: hiv-1 reverse transcriptase]]
[[Category: nnrti]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 14:55:40 2007''