2nxd: Difference between revisions
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==Structure of HIV-1 protease D25N complexed with rt-rh analogue peptide GLY-ALA-ASP-ILE-PHE*TYR-LEU-ASP-GLY-ALA== | ==Structure of HIV-1 protease D25N complexed with rt-rh analogue peptide GLY-ALA-ASP-ILE-PHE*TYR-LEU-ASP-GLY-ALA== | ||
<StructureSection load='2nxd' size='340' side='right' caption='[[2nxd]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='2nxd' size='340' side='right'caption='[[2nxd]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2nxd]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2nxd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hiv-1 Hiv-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NXD FirstGlance]. <br> | ||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1kjg|1kjg]], [[2nxl|2nxl]], [[2nxm|2nxm]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1kjg|1kjg]], [[2nxl|2nxl]], [[2nxm|2nxm]]</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=11685 HIV-1])</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=2nxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nxd OCA], [https://pdbe.org/2nxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nxd RCSB], [https://www.ebi.ac.uk/pdbsum/2nxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nxd ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nx/2nxd_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nx/2nxd_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
| Line 30: | Line 30: | ||
==See Also== | ==See Also== | ||
*[[Immunodeficiency virus protease|Immunodeficiency virus protease]] | *[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
[[Category: Hiv-1]] | [[Category: Hiv-1]] | ||
[[Category: Large Structures]] | |||
[[Category: Nalivaika, E]] | [[Category: Nalivaika, E]] | ||
[[Category: Prabu-Jeyabalan, M]] | [[Category: Prabu-Jeyabalan, M]] | ||
Revision as of 18:53, 8 June 2021
Structure of HIV-1 protease D25N complexed with rt-rh analogue peptide GLY-ALA-ASP-ILE-PHE*TYR-LEU-ASP-GLY-ALAStructure of HIV-1 protease D25N complexed with rt-rh analogue peptide GLY-ALA-ASP-ILE-PHE*TYR-LEU-ASP-GLY-ALA
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedDrug resistance in HIV-1 protease, a barrier to effective treatment, is generally caused by mutations in the enzyme that disrupt inhibitor binding but still allow for substrate processing. Structural studies with mutant, inactive enzyme, have provided detailed information regarding how the substrates bind to the protease yet avoid resistance mutations; insights obtained inform the development of next generation therapeutics. Although structures have been obtained of complexes between substrate peptide and inactivated (D25N) protease, thermodynamic studies of peptide binding have been challenging due to low affinity. Peptides that bind tighter to the inactivated protease than the natural substrates would be valuable for thermodynamic studies as well as to explore whether the structural envelope observed for substrate peptides is a function of weak binding. Here, two computational methods-namely, charge optimization and protein design-were applied to identify peptide sequences predicted to have higher binding affinity to the inactivated protease, starting from an RT-RH derived substrate peptide. Of the candidate designed peptides, three were tested for binding with isothermal titration calorimetry, with one, containing a single threonine to valine substitution, measured to have more than a 10-fold improvement over the tightest binding natural substrate. Crystal structures were also obtained for the same three designed peptide complexes; they show good agreement with computational prediction. Thermodynamic studies show that binding is entropically driven, more so for designed affinity enhanced variants than for the starting substrate. Structural studies show strong similarities between natural and tighter-binding designed peptide complexes, which may have implications in understanding the molecular mechanisms of drug resistance in HIV-1 protease. Computational design and experimental study of tighter binding peptides to an inactivated mutant of HIV-1 protease.,Altman MD, Nalivaika EA, Prabu-Jeyabalan M, Schiffer CA, Tidor B Proteins. 2008 Feb 15;70(3):678-94. PMID:17729291[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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