6qfh
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of Human Kallikrein 6 (N217D/I218Y/K224R) in complex with GSK144.== | |
| + | <StructureSection load='6qfh' size='340' side='right'caption='[[6qfh]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6qfh]] 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=6QFH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QFH 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]] 1.65Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J08:4-[(5-phenyl-1~{H}-imidazol-2-yl)methylamino]-2-(pyridin-3-ylmethoxy)benzenecarboximidamide'>J08</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=6qfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qfh OCA], [https://pdbe.org/6qfh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qfh RCSB], [https://www.ebi.ac.uk/pdbsum/6qfh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qfh ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/KLK6_HUMAN KLK6_HUMAN] Serine protease which exhibits a preference for Arg over Lys in the substrate P1 position and for Ser or Pro in the P2 position. Shows activity against amyloid precursor protein, myelin basic protein, gelatin, casein and extracellular matrix proteins such as fibronectin, laminin, vitronectin and collagen. Degrades alpha-synuclein and prevents its polymerization, indicating that it may be involved in the pathogenesis of Parkinson disease and other synucleinopathies. May be involved in regulation of axon outgrowth following spinal cord injury. Tumor cells treated with a neutralizing KLK6 antibody migrate less than control cells, suggesting a role in invasion and metastasis.<ref>PMID:12878203</ref> <ref>PMID:12928483</ref> <ref>PMID:15557757</ref> <ref>PMID:16987227</ref> <ref>PMID:16321973</ref> <ref>PMID:11983703</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The inhibition of kallikrein 5 (KLK5) has been identified as a potential strategy for treatment of the genetic skin disorder Netherton syndrome, in which loss-of-function mutations in the SPINK5 gene lead to down-regulation of the endogenous inhibitor LEKTI-1 and profound skin-barrier defects with severe allergic manifestations. To aid in the development of a medicine for this target, an X-ray crystallographic system was developed to facilitate fragment-guided chemistry and knowledge-based drug-discovery approaches. Here, the development of a surrogate crystallographic system in place of KLK5, which proved to be challenging to crystallize, is described. The biochemical robustness of the crystallographic surrogate and the suitability of the system for the study of small nonpeptidic fragments and lead-like molecules are demonstrated. | ||
| - | + | Evaluation of a crystallographic surrogate for kallikrein 5 in the discovery of novel inhibitors for Netherton syndrome.,Thorpe JH, Edgar EV, Smith KJ, Lewell XQ, Rella M, White GV, Polyakova O, Nassau P, Walker AL, Holmes DS, Pearce AC, Wang Y, Liddle J, Hovnanian A Acta Crystallogr F Struct Biol Commun. 2019 May 1;75(Pt 5):385-391. doi:, 10.1107/S2053230X19003169. Epub 2019 Apr 26. PMID:31045568<ref>PMID:31045568</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Thorpe | + | <div class="pdbe-citations 6qfh" style="background-color:#fffaf0;"></div> |
| + | |||
| + | ==See Also== | ||
| + | *[[Kallikrein 3D structures|Kallikrein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Thorpe JH]] | ||
Current revision
Crystal Structure of Human Kallikrein 6 (N217D/I218Y/K224R) in complex with GSK144.
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