5mb5: Difference between revisions
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==Cocktail experiment C: fragments 103 and 171 in complex with Endothiapepsin== | ==Cocktail experiment C: fragments 103 and 171 in complex with Endothiapepsin== | ||
<StructureSection load='5mb5' size='340' side='right' caption='[[5mb5]], [[Resolution|resolution]] 0.98Å' scene=''> | <StructureSection load='5mb5' size='340' side='right'caption='[[5mb5]], [[Resolution|resolution]] 0.98Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5mb5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MB5 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5mb5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MB5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MB5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=46P:4-METHYL-5-(1-METHYL-1H-IMIDAZOL-2-YL)-1,3-THIAZOL-2-AMINE'>46P</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=46P:4-METHYL-5-(1-METHYL-1H-IMIDAZOL-2-YL)-1,3-THIAZOL-2-AMINE'>46P</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3t7p|3t7p]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3t7p|3t7p]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mb5 OCA], [http://pdbe.org/5mb5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mb5 RCSB], [http://www.ebi.ac.uk/pdbsum/5mb5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mb5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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[[Category: Cryphonectria parasitica]] | [[Category: Cryphonectria parasitica]] | ||
[[Category: Endothiapepsin]] | [[Category: Endothiapepsin]] | ||
[[Category: Large Structures]] | |||
[[Category: Heine, A]] | [[Category: Heine, A]] | ||
[[Category: Klebe, G]] | [[Category: Klebe, G]] | ||
Revision as of 10:14, 19 August 2020
Cocktail experiment C: fragments 103 and 171 in complex with EndothiapepsinCocktail experiment C: fragments 103 and 171 in complex with Endothiapepsin
Structural highlights
Publication Abstract from PubMedSuccessful optimization of a given lead scaffold requires thorough binding-site mapping of the target protein particular in regions remote from the catalytic center where high conservation across protein families is given. We screened a 361-entry fragment library for binding to the aspartic protease endothiapepsin by crystallography. This enzyme is frequently used as a surrogate for the design of renin and beta-secretase inhibitors. A hit rate of 20% was achieved, providing 71 crystal structures. Here, we discuss 45 binding poses of fragments accommodated in pockets remote from the catalytic dyad. Three major hot spots are discovered in remote binding areas: Asp81, Asp119, and Phe291. Compared to the dyad binders, bulkier fragments occupy these regions. Many of the discovered fragments suggest an optimization concept on how to grow them into larger ligands occupying adjacent binding pockets that will possibly endow them with the desired selectivity for one given member of a protein family. Experimental Active-Site Mapping by Fragments: Hot Spots Remote from the Catalytic Center of Endothiapepsin.,Radeva N, Krimmer SG, Stieler M, Fu K, Wang X, Ehrmann FR, Metz A, Huschmann FU, Weiss MS, Mueller U, Schiebel J, Heine A, Klebe G J Med Chem. 2016 Aug 25;59(16):7561-75. doi: 10.1021/acs.jmedchem.6b00645. Epub, 2016 Aug 12. PMID:27463859[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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