7z58: Difference between revisions
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==Crystal structure of human Cathepsin L in complex with covalently bound Calpeptin== | |||
<StructureSection load='7z58' size='340' side='right'caption='[[7z58]], [[Resolution|resolution]] 1.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7z58]] 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=7Z58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z58 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]] 1.35Å</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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=RN2:(phenylmethyl)+~{N}-[(2~{S})-4-methyl-1-[[(2~{S})-1-oxidanylhexan-2-yl]amino]-1-oxidanylidene-pentan-2-yl]carbamate'>RN2</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=7z58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z58 OCA], [https://pdbe.org/7z58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z58 RCSB], [https://www.ebi.ac.uk/pdbsum/7z58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z58 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 == | |||
Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (M(pro)), its moderate activity in M(pro) inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin's efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated Calpeptin at a dose of 1 mg/kg body weight reduces the viral load in the trachea. Despite a higher risk of side effects, an intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. Here we show that the inhibition of cathepsins, a protein family of the host organism, by calpeptin is a promising approach for the treatment of SARS-CoV-2 and potentially other viral infections. | |||
Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections.,Reinke PYA, de Souza EE, Gunther S, Falke S, Lieske J, Ewert W, Loboda J, Herrmann A, Rahmani Mashhour A, Karnicar K, Usenik A, Lindic N, Sekirnik A, Botosso VF, Santelli GMM, Kapronezai J, de Araujo MV, Silva-Pereira TT, Filho AFS, Tavares MS, Florez-Alvarez L, de Oliveira DBL, Durigon EL, Giaretta PR, Heinemann MB, Hauser M, Seychell B, Bohler H, Rut W, Drag M, Beck T, Cox R, Chapman HN, Betzel C, Brehm W, Hinrichs W, Ebert G, Latham SL, Guimaraes AMS, Turk D, Wrenger C, Meents A Commun Biol. 2023 Oct 18;6(1):1058. doi: 10.1038/s42003-023-05317-9. PMID:37853179<ref>PMID:37853179</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7z58" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Beck T]] | |||
[[Category: Boehler H]] | |||
[[Category: Chapman HN]] | |||
[[Category: Cox R]] | |||
[[Category: Ewert W]] | |||
[[Category: Falke S]] | |||
[[Category: Guenther S]] | |||
[[Category: Hauser M]] | |||
[[Category: Hinrichs W]] | |||
[[Category: Karnicar K]] | |||
[[Category: Lach M]] | |||
[[Category: Lieske J]] | |||
[[Category: Lindic N]] | |||
[[Category: Loboda J]] | |||
[[Category: Meents A]] | |||
[[Category: Rahmani Mashhour A]] | |||
[[Category: Reinke PYA]] | |||
[[Category: Turk D]] | |||
[[Category: Usenik A]] | |||
Latest revision as of 09:58, 21 November 2024
Crystal structure of human Cathepsin L in complex with covalently bound CalpeptinCrystal structure of human Cathepsin L in complex with covalently bound Calpeptin
Structural highlights
FunctionCATL1_HUMAN Important for the overall degradation of proteins in lysosomes. Publication Abstract from PubMedSeveral drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (M(pro)), its moderate activity in M(pro) inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin's efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated Calpeptin at a dose of 1 mg/kg body weight reduces the viral load in the trachea. Despite a higher risk of side effects, an intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. Here we show that the inhibition of cathepsins, a protein family of the host organism, by calpeptin is a promising approach for the treatment of SARS-CoV-2 and potentially other viral infections. Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections.,Reinke PYA, de Souza EE, Gunther S, Falke S, Lieske J, Ewert W, Loboda J, Herrmann A, Rahmani Mashhour A, Karnicar K, Usenik A, Lindic N, Sekirnik A, Botosso VF, Santelli GMM, Kapronezai J, de Araujo MV, Silva-Pereira TT, Filho AFS, Tavares MS, Florez-Alvarez L, de Oliveira DBL, Durigon EL, Giaretta PR, Heinemann MB, Hauser M, Seychell B, Bohler H, Rut W, Drag M, Beck T, Cox R, Chapman HN, Betzel C, Brehm W, Hinrichs W, Ebert G, Latham SL, Guimaraes AMS, Turk D, Wrenger C, Meents A Commun Biol. 2023 Oct 18;6(1):1058. doi: 10.1038/s42003-023-05317-9. PMID:37853179[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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