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| | <StructureSection load='2qxh' size='340' side='right'caption='[[2qxh]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='2qxh' size='340' side='right'caption='[[2qxh]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qxh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QXH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qxh]] 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=2QXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QXH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K7J:N-(3-CARBOXYPROPANOYL)-L-ALANYL-L-ALANYL-N-[(2S,3S)-4-CHLORO-3-HYDROXY-1-PHENYLBUTAN-2-YL]-L-PROLINAMIDE'>K7J</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qxg|2qxg]], [[2qxi|2qxi]], [[2qxj|2qxj]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K7J:N-(3-CARBOXYPROPANOYL)-L-ALANYL-L-ALANYL-N-[(2S,3S)-4-CHLORO-3-HYDROXY-1-PHENYLBUTAN-2-YL]-L-PROLINAMIDE'>K7J</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KLK7, PRSS6, SCCE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Stratum_corneum_chymotryptic_enzyme Stratum corneum chymotryptic enzyme], with EC number [https://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=2qxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qxh OCA], [https://pdbe.org/2qxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qxh RCSB], [https://www.ebi.ac.uk/pdbsum/2qxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qxh ProSAT]</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=2qxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qxh OCA], [https://pdbe.org/2qxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qxh RCSB], [https://www.ebi.ac.uk/pdbsum/2qxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qxh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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.
| + | [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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Stratum corneum chymotryptic enzyme]]
| + | [[Category: Bode W]] |
| - | [[Category: Bode, W]] | + | [[Category: Debela M]] |
| - | [[Category: Debela, M]] | + | [[Category: Goettig P]] |
| - | [[Category: Goettig, P]] | + | [[Category: Hess P]] |
| - | [[Category: Hess, P]] | + | [[Category: Magdolen V]] |
| - | [[Category: Magdolen, V]] | + | [[Category: Schechter NM]] |
| - | [[Category: Schechter, N M]] | + | |
| - | [[Category: 70-80 loop]]
| + | |
| - | [[Category: Active site inhibitor]]
| + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Chloromethyl ketone]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| 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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
hK7 or human stratum corneum chymotryptic enzyme belongs to the human tissue kallikrein (hKs) serine proteinase family and is strongly expressed in the upper layers of the epidermis. It participates in skin desquamation but is also implicated in diverse skin diseases and is a potential biomarker of ovarian cancer. We have solved x-ray structures of recombinant active hK7 at medium and atomic resolution in the presence of the inhibitors succinyl-Ala-Ala-Pro-Phe-chloromethyl ketone and Ala-Ala-Phe-chloromethyl ketone. The most distinguishing features of hK7 are the short 70-80 loop and the unique S1 pocket, which prefers P1 Tyr residues, as shown by kinetic data. Similar to several other kallikreins, the enzyme activity is inhibited by Zn(2+) and Cu(2+) at low micromolar concentrations. Biochemical analyses of the mutants H99A and H41F confirm that only the metal-binding site at His(99) close to the catalytic triad accounts for the noncompetitive Zn(2+) inhibition type. Additionally, hK7 exhibits large positively charged surface patches, representing putative exosites for prime side substrate recognition.
Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7.,Debela M, Hess P, Magdolen V, Schechter NM, Steiner T, Huber R, Bode W, Goettig P Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16086-91. Epub 2007 Oct 1. PMID:17909180[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Debela M, Hess P, Magdolen V, Schechter NM, Steiner T, Huber R, Bode W, Goettig P. Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7. Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16086-91. Epub 2007 Oct 1. PMID:17909180
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