View source for 2r3t


==I50V HIV-1 protease mutant in complex with a carbamoyl decorated pyrrolidine-based inhibitor==
<StructureSection load='2r3t' size='340' side='right'caption='[[2r3t]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2r3t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R3T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R3T FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G4G:4,4-{(3S,4S)-PYRROLIDINE-3,4-DIYLBIS[(BENZYLIMINO)SULFONYL]}DIBENZAMIDE'>G4G</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2r38|2r38]], [[2r3w|2r3w]], [[2r43|2r43]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2r3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r3t OCA], [https://pdbe.org/2r3t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r3t RCSB], [https://www.ebi.ac.uk/pdbsum/2r3t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r3t 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/r3/2r3t_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=2r3t ConSurf].
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== Publication Abstract from PubMed ==
Human immunodeficiency virus (HIV) protease is a well-established drug target in HIV chemotherapy. However, continuously increasing resistance towards approved drugs inevitably requires the development of new inhibitors preferably showing no susceptibility against resistant HIV protease strains. Recently, symmetric pyrrolidine-3,4-bis-N-benzyl-sulfonamides have been developed as a new class of HIV-1 protease inhibitors. The most promising candidate exhibited a K(i) of 74 nM towards a wild-type protease. Herein, we report the influence of the active-site mutations Ile50Val and Ile84Val on these inhibitors by structural and kinetic analysis. Although the Ile50Val mutation leads to a significant decrease in affinity for all compounds in this series, they retain or even show increased affinity towards the important Ile84Val mutation. By detailed analysis of the crystal structures of two representatives in complex with wild-type and mutant proteases, we were able to elucidate the structural basis of this phenomenon.

Structural and kinetic analysis of pyrrolidine-based inhibitors of the drug-resistant Ile84Val mutant of HIV-1 protease.,Bottcher J, Blum A, Heine A, Diederich WE, Klebe G J Mol Biol. 2008 Nov 7;383(2):347-57. Epub 2008 Jul 29. PMID:18692068<ref>PMID:18692068</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 2r3t" style="background-color:#fffaf0;"></div>

==See Also==
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: HIV-1 retropepsin]]
[[Category: Large Structures]]
[[Category: Blum, A]]
[[Category: Boettcher, J]]
[[Category: Diederich, W E]]
[[Category: Heine, A]]
[[Category: Klebe, G]]
[[Category: Aspartyl protease]]
[[Category: Hydrolase]]
[[Category: Protease]]
[[Category: Protein-ligand complex]]