View source for 1fko

[[Image:1fko.gif|left|200px]]<br />
<applet load="1fko" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="1fko, resolution 2.9&Aring;" />
'''CRYSTAL STRUCTURE OF NNRTI RESISTANT K103N MUTANT HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH DMP-266(EFAVIRENZ)'''<br />

==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.

==About this Structure==
1FKO 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 EFZ as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1FKO OCA]. 

==Reference==
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11080630 11080630]
[[Category: Human immunodeficiency virus 1]]
[[Category: Protein complex]]
[[Category: RNA-directed DNA polymerase]]
[[Category: Milton, J.]]
[[Category: Ren, J.]]
[[Category: Short, S.A.]]
[[Category: Stammers, D.K.]]
[[Category: Stuart, D.I.]]
[[Category: Weaver, K.L.]]
[[Category: EFZ]]
[[Category: aids]]
[[Category: dmp-266]]
[[Category: drug design]]
[[Category: drug resistance mutation]]
[[Category: efavirenz]]
[[Category: hiv-1 reverse transcriptase]]
[[Category: non-nucleoside inhibitor]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 14:03:26 2007''