3kku: Difference between revisions
No edit summary |
No edit summary |
||
Line 1: | Line 1: | ||
==Cruzain in complex with a non-covalent ligand== | ==Cruzain in complex with a non-covalent ligand== | ||
<StructureSection load='3kku' size='340' side='right' caption='[[3kku]], [[Resolution|resolution]] 1.28Å' scene=''> | <StructureSection load='3kku' size='340' side='right'caption='[[3kku]], [[Resolution|resolution]] 1.28Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3kku]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycr Trycr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KKU OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[3kku]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycr Trycr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KKU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3KKU FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B95:N-[2-(1H-BENZIMIDAZOL-2-YL)ETHYL]-2-(2-BROMOPHENOXY)ACETAMIDE'>B95</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=Z22:S-METHYL+METHANESULFONOTHIOATE'>Z22</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B95:N-[2-(1H-BENZIMIDAZOL-2-YL)ETHYL]-2-(2-BROMOPHENOXY)ACETAMIDE'>B95</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=Z22:S-METHYL+METHANESULFONOTHIOATE'>Z22</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cruzipain Cruzipain], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.51 3.4.22.51] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cruzipain Cruzipain], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.51 3.4.22.51] </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=3kku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kku OCA], [http://pdbe.org/3kku PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kku RCSB], [http://www.ebi.ac.uk/pdbsum/3kku PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kku ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
Line 37: | Line 37: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Cruzipain]] | [[Category: Cruzipain]] | ||
[[Category: Large Structures]] | |||
[[Category: Trycr]] | [[Category: Trycr]] | ||
[[Category: Eidam, O]] | [[Category: Eidam, O]] |
Revision as of 10:02, 7 October 2020
Cruzain in complex with a non-covalent ligandCruzain in complex with a non-covalent ligand
Structural highlights
Function[CYSP_TRYCR] Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys; requires at least one more amino acid, preferably Arg, Phe, Val or Leu, between the terminal Arg or Lys and the amino-blocking group. The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle. 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 PubMedVirtual and high-throughput screens (HTS) should have complementary strengths and weaknesses, but studies that prospectively and comprehensively compare them are rare. We undertook a parallel docking and HTS screen of 197861 compounds against cruzain, a thiol protease target for Chagas disease, looking for reversible, competitive inhibitors. On workup, 99% of the hits were eliminated as false positives, yielding 146 well-behaved, competitive ligands. These fell into five chemotypes: two were prioritized by scoring among the top 0.1% of the docking-ranked library, two were prioritized by behavior in the HTS and by clustering, and one chemotype was prioritized by both approaches. Determination of an inhibitor/cruzain crystal structure and comparison of the high-scoring docking hits to experiment illuminated the origins of docking false-negatives and false-positives. Prioritizing molecules that are both predicted by docking and are HTS-active yields well-behaved molecules, relatively unobscured by the false-positives to which both techniques are individually prone. Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors.,Ferreira RS, Simeonov A, Jadhav A, Eidam O, Mott BT, Keiser MJ, McKerrow JH, Maloney DJ, Irwin JJ, Shoichet BK J Med Chem. 2010 Jul 8;53(13):4891-905. PMID:20540517[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
|