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==Structure of Cathepsin S in complex with Compound 1== | ==Structure of Cathepsin S in complex with Compound 1== | ||
<StructureSection load='6yyo' size='340' side='right'caption='[[6yyo]]' scene=''> | <StructureSection load='6yyo' size='340' side='right'caption='[[6yyo]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YYO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YYO FirstGlance]. <br> | <table><tr><td colspan='2'>[[6yyo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YYO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YYO FirstGlance]. <br> | ||
</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=6yyo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yyo OCA], [https://pdbe.org/6yyo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yyo RCSB], [https://www.ebi.ac.uk/pdbsum/6yyo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yyo ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=Q1K:6-(4-methylsulfonylpiperazin-1-yl)-[1,2,4]triazolo[4,3-b]pyridazine'>Q1K</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6yyo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yyo OCA], [https://pdbe.org/6yyo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yyo RCSB], [https://www.ebi.ac.uk/pdbsum/6yyo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yyo ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/CATS_HUMAN CATS_HUMAN] Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L and cathepsin N. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization. | |||
Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors.,Schade M, Merla B, Lesch B, Wagener M, Timmermanns S, Pletinckx K, Hertrampf T J Med Chem. 2020 Oct 22;63(20):11801-11808. doi: 10.1021/acs.jmedchem.0c00949. , Epub 2020 Sep 17. PMID:32880457<ref>PMID:32880457</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6yyo" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cathepsin 3D structures|Cathepsin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Hars U]] | [[Category: Hars U]] | ||
Revision as of 13:20, 24 November 2022
Structure of Cathepsin S in complex with Compound 1Structure of Cathepsin S in complex with Compound 1
Structural highlights
FunctionCATS_HUMAN Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L and cathepsin N. Publication Abstract from PubMedPharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization. Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors.,Schade M, Merla B, Lesch B, Wagener M, Timmermanns S, Pletinckx K, Hertrampf T J Med Chem. 2020 Oct 22;63(20):11801-11808. doi: 10.1021/acs.jmedchem.0c00949. , Epub 2020 Sep 17. PMID:32880457[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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