1fko

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[[Image:1fko.gif|left|200px]]<br /><applet load="1fko" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1fko.gif|left|200px]]
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caption="1fko, resolution 2.9&Aring;" />
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'''CRYSTAL STRUCTURE OF NNRTI RESISTANT K103N MUTANT HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH DMP-266(EFAVIRENZ)'''<br />
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{{Structure
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|PDB= 1fko |SIZE=350|CAPTION= <scene name='initialview01'>1fko</scene>, resolution 2.9&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=EFZ:(-)-6-CHLORO-4-CYCLOPROPYLETHYNYL-4-TRIFLUOROMETHYL-1,4-DIHYDRO-2H-3,1-BENZOXAZIN-2-ONE'>EFZ</scene>
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|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]
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|GENE=
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}}
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'''CRYSTAL STRUCTURE OF NNRTI RESISTANT K103N MUTANT HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH DMP-266(EFAVIRENZ)'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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 <scene name='pdbligand=EFZ:'>EFZ</scene> 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://oca.weizmann.ac.il/oca-bin/ocashort?id=1FKO OCA].
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1FKO 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=1FKO OCA].
==Reference==
==Reference==
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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]
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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://www.ncbi.nlm.nih.gov/pubmed/11080630 11080630]
[[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: EFZ]]
[[Category: EFZ]]
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[[Category: aids]]
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[[Category: aid]]
[[Category: dmp-266]]
[[Category: dmp-266]]
[[Category: drug design]]
[[Category: drug design]]
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[[Category: non-nucleoside inhibitor]]
[[Category: non-nucleoside inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:39:40 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:10:19 2008''

Revision as of 09:10, 20 March 2008

Image:1fko.gif


PDB ID 1fko

Drag the structure with the mouse to rotate
, resolution 2.9Å
Ligands:
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 DMP-266(EFAVIRENZ)


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 Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from 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:11080630

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