View source for 2fnt


==Crystal structure of a drug-resistant (V82A) inactive (D25N) HIV-1 protease complexed with AP2V variant of HIV-1 NC-p1 substrate.==
<StructureSection load='2fnt' size='340' side='right' caption='[[2fnt]], [[Resolution|resolution]] 1.44&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2fnt]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FNT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FNT FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tsq|1tsq]], [[2fns|2fns]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fnt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fnt OCA], [http://pdbe.org/2fnt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fnt RCSB], [http://www.ebi.ac.uk/pdbsum/2fnt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2fnt ProSAT]</span></td></tr>
</table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fn/2fnt_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2fnt ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Human immunodeficiency virus type 1 (HIV-1) protease processes and cleaves the Gag and Gag-Pol polyproteins, allowing viral maturation, and therefore is an important target for antiviral therapy. Ligand binding occurs when the flaps open, allowing access to the active site. This flexibility in flap geometry makes trapping and crystallizing structural intermediates in substrate binding challenging. In this study, we report two crystal structures of two HIV-1 protease variants bound with their corresponding nucleocapsid-p1 variant. One of the flaps in each of these structures exhibits an unusual "intermediate" conformation. Analysis of the flap-intermediate and flap-closed crystal structures reveals that the intermonomer flap movements may be asynchronous and that the flap which wraps over the P3 to P1 (P3-P1) residues of the substrate might close first. This is consistent with our hypothesis that the P3-P1 region is crucial for substrate recognition. The intermediate conformation is conserved in both the wild-type and drug-resistant variants. The structural differences between the variants are evident only when the flaps are closed. Thus, a plausible structural model for the adaptability of HIV-1 protease to recognize substrates in the presence of drug-resistant mutations has been proposed.

Mechanism of substrate recognition by drug-resistant human immunodeficiency virus type 1 protease variants revealed by a novel structural intermediate.,Prabu-Jeyabalan M, Nalivaika EA, Romano K, Schiffer CA J Virol. 2006 Apr;80(7):3607-16. PMID:16537628<ref>PMID:16537628</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2fnt" style="background-color:#fffaf0;"></div>

==See Also==
*[[Immunodeficiency virus protease|Immunodeficiency virus protease]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: HIV-1 retropepsin]]
[[Category: Nalivaika, E A]]
[[Category: Prabu-Jeyabaln, M]]
[[Category: Schiffer, C A]]
[[Category: Drug resistance]]
[[Category: Flap conformation]]
[[Category: Hiv-1 protease]]
[[Category: Hydrolase]]
[[Category: Nc-p1 substrate]]
[[Category: Structural intermediate]]
[[Category: Substrate recognition]]