2p3b: Difference between revisions

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-{{Seed}}
-[[Image:2p3b.png|left|200px]]
-<!--
+==Crystal Structure of the subtype B wild type HIV protease complexed with TL-3 inhibitor==
-The line below this paragraph, containing "STRUCTURE_2p3b", creates the "Structure Box" on the page.
+<StructureSection load='2p3b' size='340' side='right'caption='[[2p3b]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2p3b]] is a 2 chain structure with sequence from [https://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=2P3B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P3B FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3TL:BENZYL+[(1S,4S,7S,8R,9R,10S,13S,16S)-7,10-DIBENZYL-8,9-DIHYDROXY-1,16-DIMETHYL-4,13-BIS(1-METHYLETHYL)-2,5,12,15,18-PENTAOXO-20-PHENYL-19-OXA-3,6,11,14,17-PENTAAZAICOS-1-YL]CARBAMATE'>3TL</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
-{{STRUCTURE_2p3b|  PDB=2p3b  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2p3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p3b OCA], [https://pdbe.org/2p3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p3b RCSB], [https://www.ebi.ac.uk/pdbsum/2p3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p3b ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q9Q2G8_9HIV1 Q9Q2G8_9HIV1]
+== 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/p3/2p3b_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2p3b ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Although a majority of HIV-1 infections in Brazil are caused by the subtype B virus (also prevalent in the United States and Western Europe), viral subtypes F and C are also found very frequently. Genomic differences between the subtypes give rise to sequence variations in the encoded proteins, including the HIV-1 protease. The current anti-HIV drugs have been developed primarily against subtype B and the effects arising from the combination of drug-resistance mutations with the naturally existing polymorphisms in non-B HIV-1 subtypes are only beginning to be elucidated. To gain more insights into the structure and function of different variants of HIV proteases, we have determined a 2.1 A structure of the native subtype F HIV-1 protease (PR) in complex with the protease inhibitor TL-3. We have also solved crystal structures of two multi-drug resistant mutant HIV PRs in complex with TL-3, from subtype B (Bmut) carrying the primary mutations V82A and L90M, and from subtype F (Fmut) carrying the primary mutation V82A plus the secondary mutation M36I, at 1.75 A and 2.8 A resolution, respectively. The proteases Bmut, Fwt and Fmut exhibit sevenfold, threefold, and 54-fold resistance to TL-3, respectively. In addition, the structure of subtype B wild type HIV-PR in complex with TL-3 has been redetermined in space group P6(1), consistent with the other three structures. Our results show that the primary mutation V82A causes the known effect of collapsing the S1/S1' pockets that ultimately lead to the reduced inhibitory effect of TL-3. Our results further indicate that two naturally occurring polymorphic substitutions in subtype F and other non-B HIV proteases, M36I and L89M, may lead to early development of drug resistance in patients infected with non-B HIV subtypes.
-===Crystal Structure of the subtype B wild type HIV protease complexed with TL-3 inhibitor===
+Structural characterization of B and non-B subtypes of HIV-protease: insights into the natural susceptibility to drug resistance development.,Sanches M, Krauchenco S, Martins NH, Gustchina A, Wlodawer A, Polikarpov I J Mol Biol. 2007 Jun 15;369(4):1029-40. Epub 2007 Mar 24. PMID:17467738<ref>PMID:17467738</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2p3b" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_17467738}}, adds the Publication Abstract to the page
+*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 17467738 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_17467738}}
+__TOC__
+</StructureSection>
-==About this Structure==
-P3B 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=2P3B OCA].
-==Reference==
-Structural characterization of B and non-B subtypes of HIV-protease: insights into the natural susceptibility to drug resistance development., Sanches M, Krauchenco S, Martins NH, Gustchina A, Wlodawer A, Polikarpov I, J Mol Biol. 2007 Jun 15;369(4):1029-40. Epub 2007 Mar 24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17467738 17467738]
-[[Category: HIV-1 retropepsin]]
 [[Category: Human immunodeficiency virus 1]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Gustchina, A.]]
+[[Category: Gustchina A]]
-[[Category: Krauchenco, S.]]
+[[Category: Krauchenco S]]
-[[Category: Martins, N H.]]
+[[Category: Martins NH]]
-[[Category: Polikarpov, I.]]
+[[Category: Polikarpov I]]
-[[Category: Sanches, M.]]
+[[Category: Sanches M]]
-[[Category: Wlodawer, A.]]
+[[Category: Wlodawer A]]
-[[Category: Protease-inhibitor complex]]
-[[Category: Tl-3 inhibitor]]
-[[Category: Wild type subtype b hiv protease]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 15:36:42 2008''