View source for 8a4u


==Crystal structure of human cathepsin L with CAA0225==
<StructureSection load='8a4u' size='340' side='right'caption='[[8a4u]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8a4u]] is a 4 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=8A4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A4U 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=L2X:(2~{S},3~{S})-~{N}3-[2-(4-hydroxyphenyl)ethyl]-~{N}2-[(2~{S})-1-oxidanylidene-3-phenyl-1-[(phenylmethyl)amino]propan-2-yl]oxirane-2,3-dicarboxamide'>L2X</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=8a4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a4u OCA], [https://pdbe.org/8a4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a4u RCSB], [https://www.ebi.ac.uk/pdbsum/8a4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a4u ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CATL1_HUMAN CATL1_HUMAN] Important for the overall degradation of proteins in lysosomes.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Emerging RNA viruses, including SARS-CoV-2, continue to be a major threat. Cell entry of SARS-CoV-2 particles via the endosomal pathway involves cysteine cathepsins. Due to ubiquitous expression, cathepsin L (CatL) is considered a promising drug target in the context of different viral and lysosome-related diseases. We characterized the anti-SARS-CoV-2 activity of a set of carbonyl- and succinyl epoxide-based inhibitors, which were previously identified as inhibitors of cathepsins or related cysteine proteases. Calpain inhibitor XII, MG-101, and CatL inhibitor IV possess antiviral activity in the very low nanomolar EC(50) range in Vero E6 cells and inhibit CatL in the picomolar K(i) range. We show a relevant off-target effect of CatL inhibition by the coronavirus main protease alpha-ketoamide inhibitor 13b. Crystal structures of CatL in complex with 14 compounds at resolutions better than 2 A present a solid basis for structure-guided understanding and optimization of CatL inhibitors toward protease drug development.

Structural Elucidation and Antiviral Activity of Covalent Cathepsin L Inhibitors.,Falke S, Lieske J, Herrmann A, Loboda J, Karnicar K, Gunther S, Reinke PYA, Ewert W, Usenik A, Lindic N, Sekirnik A, Dretnik K, Tsuge H, Turk V, Chapman HN, Hinrichs W, Ebert G, Turk D, Meents A J Med Chem. 2024 May 9;67(9):7048-7067. doi: 10.1021/acs.jmedchem.3c02351. Epub , 2024 Apr 17. PMID:38630165<ref>PMID:38630165</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8a4u" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chapman HN]]
[[Category: Ewert W]]
[[Category: Falke S]]
[[Category: Guenther S]]
[[Category: Hinrichs W]]
[[Category: Karnicar K]]
[[Category: Lieske J]]
[[Category: Lindic N]]
[[Category: Loboda J]]
[[Category: Meents A]]
[[Category: Reinke PYA]]
[[Category: Sekirnik A]]
[[Category: Turk D]]
[[Category: Usenik A]]