View source for 5yjk


==Human kallikrein 7 in complex with 1,4-diazepane-7-one 1-acetamide derivative==
<StructureSection load='5yjk' size='340' side='right'caption='[[5yjk]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</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='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>
</table>
== Function ==
[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.
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== 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<ref>PMID:29102227</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5yjk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Kallikrein 3D structures|Kallikrein 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sugawara H]]