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| | <StructureSection load='5yjk' size='340' side='right'caption='[[5yjk]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='5yjk' size='340' side='right'caption='[[5yjk]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5yjk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YJK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5YJK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5yjk]] is a 1 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=5YJK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YJK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8VX:(R)-2-(6-(5-chloro-2-methoxybenzyl)-3-(2,2-dimethylhydrazono)-7-oxo-1,4-diazepan-1-yl)-N-(3-(methylsulfonyl)phenyl)acetamide'>8VX</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5y9l|5y9l]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8VX:2-[(3~{Z},6~{R})-6-[(5-chloranyl-2-methoxy-phenyl)methyl]-3-(dimethylhydrazinylidene)-7-oxidanylidene-1,4-diazepan-1-yl]-~{N}-(3-methylsulfonylphenyl)ethanamide'>8VX</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5yjk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yjk OCA], [https://pdbe.org/5yjk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yjk RCSB], [https://www.ebi.ac.uk/pdbsum/5yjk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yjk ProSAT]</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=5yjk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yjk OCA], [http://pdbe.org/5yjk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yjk RCSB], [http://www.ebi.ac.uk/pdbsum/5yjk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yjk 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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Stratum corneum chymotryptic enzyme]]
| + | [[Category: Sugawara H]] |
| - | [[Category: Sugawara, H]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inhibitor complex]]
| + | |
| - | [[Category: 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
Compound 1, composed of a 1,3,6-trisubstituted 1,4-diazepane-7-one, was discovered as a novel human kallikrein 7 (KLK7, stratum corneum chymotryptic enzyme, SCCE) inhibitor, and its derivatives were synthesized and evaluated. Structure-activity relationship studies of the amidoxime unit and benzoic acid part of this new scaffold led to the identification of 25 and 34, which were more potent than the hit compound, 1. The X-ray co-crystal structure of compound 25 and human KLK7 revealed the characteristic interactions and enabled explanations of the structure-activity relationship.
Discovery and structure-activity relationship study of 1,3,6-trisubstituted 1,4-diazepane-7-ones as novel human kallikrein 7 inhibitors.,Murafuji H, Sakai H, Goto M, Imajo S, Sugawara H, Muto T Bioorg Med Chem Lett. 2017 Dec 1;27(23):5272-5276. doi:, 10.1016/j.bmcl.2017.10.030. Epub 2017 Oct 17. PMID:29102227[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Murafuji H, Sakai H, Goto M, Imajo S, Sugawara H, Muto T. Discovery and structure-activity relationship study of 1,3,6-trisubstituted 1,4-diazepane-7-ones as novel human kallikrein 7 inhibitors. Bioorg Med Chem Lett. 2017 Dec 1;27(23):5272-5276. doi:, 10.1016/j.bmcl.2017.10.030. Epub 2017 Oct 17. PMID:29102227 doi:http://dx.doi.org/10.1016/j.bmcl.2017.10.030
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