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| | <StructureSection load='6y4s' size='340' side='right'caption='[[6y4s]], [[Resolution|resolution]] 2.23Å' scene=''> | | <StructureSection load='6y4s' size='340' side='right'caption='[[6y4s]], [[Resolution|resolution]] 2.23Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6y4s]] is a 3 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=6Y4S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Y4S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6y4s]] is a 3 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=6Y4S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y4S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.23Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bsq|3bsq]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KLK7, PRSS6, SCCE ([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=6y4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y4s OCA], [https://pdbe.org/6y4s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y4s RCSB], [https://www.ebi.ac.uk/pdbsum/6y4s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y4s 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/Stratum_corneum_chymotryptic_enzyme Stratum corneum chymotryptic enzyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.117 3.4.21.117] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6y4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y4s OCA], [http://pdbe.org/6y4s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6y4s RCSB], [http://www.ebi.ac.uk/pdbsum/6y4s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6y4s ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KLK7_HUMAN KLK7_HUMAN]] May catalyze the degradation of intercellular cohesive structures in the cornified layer of the skin in the continuous shedding of cells from the skin surface. Specific for amino acid residues with aromatic side chains in the P1 position. SCCE cleaves insulin B chain at '6-Leu-|-Cys-7', '16-Tyr-|-Leu-17', '25-Phe-|-Tyr-26' and '26-Tyr-|-Thr-27'. Could play a role in the activation of precursors to inflammatory cytokines. | + | [https://www.uniprot.org/uniprot/KLK7_HUMAN KLK7_HUMAN] May catalyze the degradation of intercellular cohesive structures in the cornified layer of the skin in the continuous shedding of cells from the skin surface. Specific for amino acid residues with aromatic side chains in the P1 position. SCCE cleaves insulin B chain at '6-Leu-|-Cys-7', '16-Tyr-|-Leu-17', '25-Phe-|-Tyr-26' and '26-Tyr-|-Thr-27'. Could play a role in the activation of precursors to inflammatory cytokines. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6y4s" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6y4s" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Kallikrein 3D structures|Kallikrein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Stratum corneum chymotryptic enzyme]]
| + | [[Category: Hanke S]] |
| - | [[Category: Hanke, S]] | + | [[Category: Strater N]] |
| - | [[Category: Strater, N]] | + | |
| - | [[Category: Hk7]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Kallikrein 7]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| Structural highlights
Function
KLK7_HUMAN May catalyze the degradation of intercellular cohesive structures in the cornified layer of the skin in the continuous shedding of cells from the skin surface. Specific for amino acid residues with aromatic side chains in the P1 position. SCCE cleaves insulin B chain at '6-Leu-|-Cys-7', '16-Tyr-|-Leu-17', '25-Phe-|-Tyr-26' and '26-Tyr-|-Thr-27'. Could play a role in the activation of precursors to inflammatory cytokines.
Publication Abstract from PubMed
The serine protease kallikrein-related peptidase 7 (KLK7) is a member of the human tissue kallikreins. Its dysregulation leads to pathophysiological inflammatory processes in the skin. Furthermore, it plays a role in several types of cancer. For the treatment of KLK7-associated diseases, coumarinic esters have been developed as small molecule enzyme inhibitors. To characterize the inhibition mode of these inhibitors, we analyzed structures of the inhibited protease by X-ray crystallography. Electron density shows the inhibitors covalently attached to His57 of the catalytic triad. This confirms the irreversible character of the inhibition process. Upon inhibitor binding His57 undergoes an outward rotation thus the catalytic triad of the protease is disrupted. Besides, the halophenyl moiety of the inhibitor was absent in the final enzyme-inhibitor complex due to hydrolysis of the ester linkage. With these results, we analyze the structural basis of KLK7 inhibition by covalent attachment of aromatic coumarinic esters.
Structural studies on the inhibitory binding mode of aromatic coumarinic esters to human kallikrein-related peptidase 7.,Hanke S, Tindall C, Pippel J, Ulbricht D, Pirotte B, Reboud-Ravaux M, Heiker JT, Strater N J Med Chem. 2020 May 6. doi: 10.1021/acs.jmedchem.9b01806. PMID:32374603[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hanke S, Tindall C, Pippel J, Ulbricht D, Pirotte B, Reboud-Ravaux M, Heiker JT, Strater N. Structural studies on the inhibitory binding mode of aromatic coumarinic esters to human kallikrein-related peptidase 7. J Med Chem. 2020 May 6. doi: 10.1021/acs.jmedchem.9b01806. PMID:32374603 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01806
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