5lws: Difference between revisions
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<StructureSection load='5lws' size='340' side='right'caption='[[5lws]], [[Resolution|resolution]] 1.03Å' scene=''> | <StructureSection load='5lws' size='340' side='right'caption='[[5lws]], [[Resolution|resolution]] 1.03Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5lws]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5lws]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LWS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LWS FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7B2:4-[12-[(1-chloranyl-5,6,7-trimethyl-pyrrolo[3,4-d]pyridazin-3-ium-3-yl)methyl]-10,11-dimethyl-3,4,6,7,11-pentazatricyclo[7.3.0.0^{2,6}]dodeca-1(12),2,4,7,9-pentaen-5-yl]-1,2,5-trimethyl-pyrrole-3-carbaldehyde'>7B2</scene>, <scene name='pdbligand=7B4:4-chloranyl-5,6,7-trimethyl-pyrrolo[3,4-d]pyridazine'>7B4</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TFA:TRIFLUOROACETIC+ACID'>TFA</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.03Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7B2:4-[12-[(1-chloranyl-5,6,7-trimethyl-pyrrolo[3,4-d]pyridazin-3-ium-3-yl)methyl]-10,11-dimethyl-3,4,6,7,11-pentazatricyclo[7.3.0.0^{2,6}]dodeca-1(12),2,4,7,9-pentaen-5-yl]-1,2,5-trimethyl-pyrrole-3-carbaldehyde'>7B2</scene>, <scene name='pdbligand=7B4:4-chloranyl-5,6,7-trimethyl-pyrrolo[3,4-d]pyridazine'>7B4</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TFA:TRIFLUOROACETIC+ACID'>TFA</scene></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=5lws FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lws OCA], [https://pdbe.org/5lws PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lws RCSB], [https://www.ebi.ac.uk/pdbsum/5lws PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lws ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5lws" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5lws" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Pepsin|Pepsin]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Cryphonectria parasitica]] | [[Category: Cryphonectria parasitica]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Heine | [[Category: Heine A]] | ||
[[Category: Klebe | [[Category: Klebe G]] | ||
[[Category: Schiebel | [[Category: Schiebel J]] | ||
Latest revision as of 21:54, 18 October 2023
Endothiapepsin in complex with fragment 177 and a derivative thereofEndothiapepsin in complex with fragment 177 and a derivative thereof
Structural highlights
FunctionPublication Abstract from PubMedWith the rising popularity of fragment-based approaches in drug development, more and more attention has to be devoted to the detection of false-positive screening results. In particular, the small size and low affinity of fragments drives screening techniques to their limit. The pursuit of a false-positive hit can cause significant loss of time and resources. Here, we present an instructive and intriguing investigation into the origin of misleading assay results for a fragment that emerged as the most potent binder for the aspartic protease endothiapepsin (EP) across multiple screening assays. This molecule shows its biological effect mainly after conversion into another entity through a reaction cascade that involves major rearrangements of its heterocyclic scaffold. The formed ligand binds EP through an induced-fit mechanism involving remarkable electrostatic interactions. Structural information in the initial screening proved to be crucial for the identification of this false-positive hit. A False-Positive Screening Hit in Fragment-Based Lead Discovery: Watch out for the Red Herring.,Cramer J, Schiebel J, Wulsdorf T, Grohe K, Najbauer EE, Ehrmann FR, Radeva N, Zitzer N, Linne U, Linser R, Heine A, Klebe G Angew Chem Int Ed Engl. 2017 Feb 6;56(7):1908-1913. doi: 10.1002/anie.201609824. , Epub 2017 Jan 18. PMID:28097765[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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