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| | ==Cathepsin S in complex with a covalent inhibitor with an aldehyde warhead== | | ==Cathepsin S in complex with a covalent inhibitor with an aldehyde warhead== |
| - | <StructureSection load='3ovx' size='340' side='right' caption='[[3ovx]], [[Resolution|resolution]] 1.49Å' scene=''> | + | <StructureSection load='3ovx' size='340' side='right'caption='[[3ovx]], [[Resolution|resolution]] 1.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ovx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OVX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ovx]] 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=3OVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OVX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=O64:2-CHLORO-N-[(1S)-1-FORMYLPROPYL]-3-(TRIFLUOROMETHYL)BENZAMIDE'>O64</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.49Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ovz|3ovz]]</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=O64:2-CHLORO-N-[(1S)-1-FORMYLPROPYL]-3-(TRIFLUOROMETHYL)BENZAMIDE'>O64</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTSS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3ovx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ovx OCA], [https://pdbe.org/3ovx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ovx RCSB], [https://www.ebi.ac.uk/pdbsum/3ovx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ovx ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_S Cathepsin S], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.27 3.4.22.27] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ovx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ovx OCA], [http://pdbe.org/3ovx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ovx RCSB], [http://www.ebi.ac.uk/pdbsum/3ovx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ovx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Cathepsin|Cathepsin]] | + | *[[Cathepsin 3D structures|Cathepsin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cathepsin S]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Fradera, X]] | + | [[Category: Fradera X]] |
| - | [[Category: Uitdehaag, J C.M]] | + | [[Category: Uitdehaag JCM]] |
| - | [[Category: Zeeland, M van]] | + | [[Category: Van Zeeland M]] |
| - | [[Category: Aldehyde warhead]]
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| - | [[Category: Cathepsin s]]
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| - | [[Category: Covalent inhibitor]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
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| - | [[Category: Ligand is covalently bound to cys25]]
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| - | [[Category: Lysosomeal protein]]
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| Structural highlights
Function
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.
Publication Abstract from PubMed
The trifluoromethylphenyl P2 motif from previously reported heteroarylnitrile series has been successfully applied for the design and synthesis of highly potent novel ketoamide-based cathepsin S inhibitors. The key in this process is the change of the torsion angle between the P2 phenyl ring and the attached secondary amide by adding a small Cl, F, or Me group at the 2-position.
Trifluoromethylphenyl as P2 for ketoamide-based cathepsin S inhibitors.,Cai J, Robinson J, Belshaw S, Everett K, Fradera X, van Zeeland M, van Berkom L, van Rijnsbergen P, Popplestone L, Baugh M, Dempster M, Bruin J, Hamilton W, Kinghorn E, Westwood P, Kerr J, Rankovic Z, Arbuckle W, Bennett DJ, Jones PS, Long C, Martin I, Uitdehaag JC, Meulemans T Bioorg Med Chem Lett. 2010 Dec 1;20(23):6890-4. Epub 2010 Oct 26. PMID:21030256[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cai J, Robinson J, Belshaw S, Everett K, Fradera X, van Zeeland M, van Berkom L, van Rijnsbergen P, Popplestone L, Baugh M, Dempster M, Bruin J, Hamilton W, Kinghorn E, Westwood P, Kerr J, Rankovic Z, Arbuckle W, Bennett DJ, Jones PS, Long C, Martin I, Uitdehaag JC, Meulemans T. Trifluoromethylphenyl as P2 for ketoamide-based cathepsin S inhibitors. Bioorg Med Chem Lett. 2010 Dec 1;20(23):6890-4. Epub 2010 Oct 26. PMID:21030256 doi:10.1016/j.bmcl.2010.10.012
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