1bwa: Difference between revisions

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-[[Image:1bwa.png|left|200px]]
+==HIV-1 PROTEASE (V82F/I84V) DOUBLE MUTANT COMPLEXED WITH XV638 OF DUPONT PHARMACEUTICALS==
+<StructureSection load='1bwa' size='340' side='right' caption='[[1bwa]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1bwa]] is a 2 chain structure with sequence 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=1BWA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BWA FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=XV6:[4R-(4ALPHA,5ALPHA,6BETA,7BETA)]-3,3-[[TETRAHYDRO-5,6-DIHYDROXY-2-OXO-4,7-BIS(PHENYLMETHYL)-1H-1,3-DIAZEPINE-1,3(2H)-DIYL]+BIS(METHYLENE)]BIS[N-2-THIAZOLYLBENZAMIDE]'>XV6</scene><br>
+<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bwa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1bwa RCSB], [http://www.ebi.ac.uk/pdbsum/1bwa PDBsum]</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/bw/1bwa_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/chain_selection.php?pdb_ID=2ata ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The long-term therapeutic benefit of HIV antiretroviral therapy is still threatened by drug-resistant variants. Mutations in the S1 subsite of the protease are the primary cause for the loss of sensitivity toward many HIV protease inhibitors, including our first-generation cyclic urea-based inhibitors DMP323 and DMP450. We now report the structures of the three active-site mutant proteases V82F, I84V, and V82F/I84V in complex with XV638 and SD146, two P2 analogues of DMP323 that are 8-fold more potent against the wild type and are able to inhibit a broad panel of drug-resistant variants [Jadhav, P. K., et al. (1997) J. Med. Chem. 40, 181-191]. The increased efficacy of XV638 and SD146 is due primarily to an increase in P2-S2 interactions: 30-40% more van der Waals contacts and two to four additional hydrogen bonds. Furthermore, because these new interactions do not perturb other subsites in the protease, it appears that the large complementary surface areas of their P2 substituents compensate for the loss of P1-S1 interactions and reduce the probability of selecting for drug-resistant variants.
-{{STRUCTURE_1bwa|  PDB=1bwa  |  SCENE=  }}
+Counteracting HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with XV638 and SD146, cyclic urea amides with broad specificities.,Ala PJ, Huston EE, Klabe RM, Jadhav PK, Lam PY, Chang CH Biochemistry. 1998 Oct 27;37(43):15042-9. PMID:9790666<ref>PMID:9790666</ref>
-===HIV-1 PROTEASE (V82F/I84V) DOUBLE MUTANT COMPLEXED WITH XV638 OF DUPONT PHARMACEUTICALS===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_9790666}}
+== References ==
+<references/>
-==About this Structure==
+__TOC__
-[[1bwa]] is a 2 chain structure with sequence 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=1BWA OCA].
+</StructureSection>
-==Reference==
-<ref group="xtra">PMID:009790666</ref><references group="xtra"/>
 [[Category: HIV-1 retropepsin]]
 [[Category: Human immunodeficiency virus 1]]