3oxc: Difference between revisions
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==Wild Type HIV-1 Protease with Antiviral Drug Saquinavir== | ==Wild Type HIV-1 Protease with Antiviral Drug Saquinavir== | ||
<StructureSection load='3oxc' size='340' side='right' caption='[[3oxc]], [[Resolution|resolution]] 1.16Å' scene=''> | <StructureSection load='3oxc' size='340' side='right'caption='[[3oxc]], [[Resolution|resolution]] 1.16Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3oxc]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3oxc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/9hiv1 9hiv1]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2nmw 2nmw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OXC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=ROC:(2S)-N-[(2S,3R)-4-[(2S,3S,4AS,8AS)-3-(TERT-BUTYLCARBAMOYL)-3,4,4A,5,6,7,8,8A-OCTAHYDRO-1H-ISOQUINOLIN-2-YL]-3-HYDROXY-1-PHENYL-BUTAN-2-YL]-2-(QUINOLIN-2-YLCARBONYLAMINO)BUTANEDIAMIDE'>ROC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=ROC:(2S)-N-[(2S,3R)-4-[(2S,3S,4AS,8AS)-3-(TERT-BUTYLCARBAMOYL)-3,4,4A,5,6,7,8,8A-OCTAHYDRO-1H-ISOQUINOLIN-2-YL]-3-HYDROXY-1-PHENYL-BUTAN-2-YL]-2-(QUINOLIN-2-YLCARBONYLAMINO)BUTANEDIAMIDE'>ROC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ien|2ien]], [[3mws|3mws]], [[3nu3|3nu3]], [[3cyx|3cyx]], [[3d1x|3d1x]], [[3d1y|3d1y]], [[2nmy|2nmy]], [[2nmz|2nmz]], [[2nnk|2nnk]], [[2nnp|2nnp]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ien|2ien]], [[3mws|3mws]], [[3nu3|3nu3]], [[3cyx|3cyx]], [[3d1x|3d1x]], [[3d1y|3d1y]], [[2nmy|2nmy]], [[2nmz|2nmz]], [[2nnk|2nnk]], [[2nnp|2nnp]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([ | <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'>[ | <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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3oxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oxc OCA], [https://pdbe.org/3oxc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oxc RCSB], [https://www.ebi.ac.uk/pdbsum/3oxc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oxc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 3oxc" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3oxc" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
[[Category: Large Structures]] | |||
[[Category: Kovalevsky, A Y]] | [[Category: Kovalevsky, A Y]] | ||
[[Category: Tie, Y]] | [[Category: Tie, Y]] | ||
Revision as of 14:01, 18 May 2022
Structural highlights
Publication Abstract from PubMedSaquinavir (SQV), the first antiviral HIV-1 protease (PR) inhibitor approved for AIDS therapy, has been studied in complexes with PR and the variants PR(I) (84V) and PR(V) (82A) containing the single mutations I84V and V82A that provide resistance to all the clinical inhibitors. Atomic resolution crystal structures (0.97-1.25 A) of the SQV complexes were analyzed in comparison to the protease complexes with darunavir, a new drug that targets resistant HIV, in order to understand the molecular basis of drug resistance. PR(I) (84V) and PR(V) (82A) complexes were obtained in both the space groups P2(1)2(1)2 and P2(1)2(1)2(1), which provided experimental limits for the conformational flexibility. The SQV interactions with PR were very similar in the mutant complexes, consistent with the similar inhibition constants. The mutation from bigger to smaller amino acids allows more space to accommodate the large group at P1' of SQV, unlike the reduced interactions observed in darunavir complexes. The residues 79-82 have adjusted to accommodate the large hydrophobic groups of SQV, suggesting that these residues are intrinsically flexible and their conformation depends more on the nature of the inhibitor than on the mutations in this region. This analysis will assist with development of more effective antiviral inhibitors. Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir.,Tie Y, Kovalevsky AY, Boross P, Wang YF, Ghosh AK, Tozser J, Harrison RW, Weber IT Proteins. 2007 Apr 1;67(1):232-42. PMID:17243183[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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