5lwt: Difference between revisions
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==Endothiapepsin in complex with a methoxylated derivative of fragment 177== | |||
<StructureSection load='5lwt' size='340' side='right'caption='[[5lwt]], [[Resolution|resolution]] 1.07Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5lwt]] 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=5LWT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LWT FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.069Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7B3:4-methoxy-5,6,7-trimethyl-pyrrolo[3,4-d]pyridazine'>7B3</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'>[https://proteopedia.org/fgij/fg.htm?mol=5lwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lwt OCA], [https://pdbe.org/5lwt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lwt RCSB], [https://www.ebi.ac.uk/pdbsum/5lwt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lwt ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
With 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<ref>PMID:28097765</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Heine | <div class="pdbe-citations 5lwt" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
*[[Pepsin|Pepsin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cryphonectria parasitica]] | |||
[[Category: Large Structures]] | |||
[[Category: Heine A]] | |||
[[Category: Klebe G]] | |||
[[Category: Schiebel J]] | |||
Latest revision as of 21:54, 18 October 2023
Endothiapepsin in complex with a methoxylated derivative of fragment 177Endothiapepsin in complex with a methoxylated derivative of fragment 177
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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