3s45: Difference between revisions

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 ==wild-type HIV-2 protease with antiviral drug amprenavir==
-<StructureSection load='3s45' size='340' side='right' caption='[[3s45]], [[Resolution|resolution]] 1.51&Aring;' scene=''>
+<StructureSection load='3s45' size='340' side='right'caption='[[3s45]], [[Resolution|resolution]] 1.51&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3s45]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv2 9hiv2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S45 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S45 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3s45]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_2 Human immunodeficiency virus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S45 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S45 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=478:{3-[(4-AMINO-BENZENESULFONYL)-ISOBUTYL-AMINO]-1-BENZYL-2-HYDROXY-PROPYL}-CARBAMIC+ACID+TETRAHYDRO-FURAN-3-YL+ESTER'>478</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.51&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nu3|3nu3]], [[3ebz|3ebz]], [[3ecg|3ecg]], [[3ec0|3ec0]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=478:{3-[(4-AMINO-BENZENESULFONYL)-ISOBUTYL-AMINO]-1-BENZYL-2-HYDROXY-PROPYL}-CARBAMIC+ACID+TETRAHYDRO-FURAN-3-YL+ESTER'>478</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11709 9HIV2])</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=3s45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s45 OCA], [https://pdbe.org/3s45 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s45 RCSB], [https://www.ebi.ac.uk/pdbsum/3s45 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s45 ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-2_retropepsin HIV-2 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.47 3.4.23.47] </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=3s45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s45 OCA], [http://pdbe.org/3s45 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3s45 RCSB], [http://www.ebi.ac.uk/pdbsum/3s45 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3s45 ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/Q9W9R3_9HIV2 Q9W9R3_9HIV2]
-Clinical inhibitor amprenavir (APV) is less effective on HIV-2 protease (PR) than on HIV-1 protease (PR). We solved the crystal structure of PR with APV at 1.5 A resolution to identify structural changes associated with the lowered inhibition. Furthermore, we analyzed the PR mutant (PR(1M) ) with substitutions V32I, I47V, and V82I that mimic the inhibitor binding site of PR. PR(1M) more closely resembled PR than PR in catalytic efficiency on four substrate peptides and inhibition by APV, whereas few differences were seen for two other substrates and inhibition by saquinavir (SQV) and darunavir (DRV). High resolution crystal structures of PR(1M) with APV, DRV, and SQV were compared with available PR and PR complexes. Val/Ile32 and Ile/Val47 showed compensating interactions with SQV in PR(1M) and PR, however, Ile82 interacted with a second SQV bound in an extension of the active site cavity of PR(1M). Residues 32 and 82 maintained similar interactions with DRV and APV in all the enzymes, whereas Val47 and Ile47 had opposing effects in the two subunits. Significantly diminished interactions were seen for the aniline of APV bound in PR (M) and PR relative to the strong hydrogen bonds observed in PR, consistent with 15- and 19-fold weaker inhibition, respectively. Overall, PR(1M) partially replicates the specificity of PR and gives insight into drug resistant mutations at residues 32, 47, and 82. Moreover, this analysis provides a structural explanation for the weaker antiviral effects of APV on HIV-2.
-Critical differences in HIV-1 and HIV-2 protease specificity for clinical inhibitors.,Tie Y, Wang YF, Boross PI, Chiu TY, Ghosh AK, Tozser J, Louis JM, Harrison RW, Weber IT Protein Sci. 2012 Mar;21(3):339-50. doi: 10.1002/pro.2019. Epub 2012 Jan 24. PMID:22238126<ref>PMID:22238126</ref>
+==See Also==
+*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 3s45" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: HIV-2 retropepsin]]
+[[Category: Human immunodeficiency virus 2]]
-[[Category: Tie, Y F]]
+[[Category: Large Structures]]
-[[Category: Wang, Y F]]
+[[Category: Tie Y-F]]
-[[Category: Weber, I T]]
+[[Category: Wang Y-F]]
-[[Category: Amprenavir]]
+[[Category: Weber IT]]
-[[Category: Aspartic protease]]
-[[Category: Drug resistance]]
-[[Category: Hiv/aid]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Molecular recognition]]