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<StructureSection load='3vfe' size='340' side='right'caption='[[3vfe]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
<StructureSection load='3vfe' size='340' side='right'caption='[[3vfe]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3vfe]] 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=3VFE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VFE FirstGlance]. <br>
<table><tr><td colspan='2'>[[3vfe]] 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=3VFE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VFE FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0HL:4-{[(3R)-3-{[(7-METHOXYNAPHTHALEN-2-YL)SULFONYL](THIOPHEN-3-YLMETHYL)AMINO}-2-OXOPYRROLIDIN-1-YL]METHYL}THIOPHENE-2-CARBOXIMIDAMIDE'>0HL</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]] 1.88&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KLK6, PRSS18, PRSS9 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0HL:4-{[(3R)-3-{[(7-METHOXYNAPHTHALEN-2-YL)SULFONYL](THIOPHEN-3-YLMETHYL)AMINO}-2-OXOPYRROLIDIN-1-YL]METHYL}THIOPHENE-2-CARBOXIMIDAMIDE'>0HL</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=3vfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vfe OCA], [https://pdbe.org/3vfe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vfe RCSB], [https://www.ebi.ac.uk/pdbsum/3vfe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vfe 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=3vfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vfe OCA], [https://pdbe.org/3vfe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vfe RCSB], [https://www.ebi.ac.uk/pdbsum/3vfe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vfe ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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> 
[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 ==
A series of hK6 inhibitors with a para-amidobenzylamine P1 group and a 2-hydroxybenzamide scaffold linker was discovered through virtual screening. The X-ray structure of hK6 complexed with compound 9b was determined to a resolution of 1.68A. The tertiary folding of the hK6 complexed with the inhibitor is conserved relative to the structure of the apo-protein, whereas the interaction between hK6 and the inhibitor is consistent with both the SAR and the in silico model used in the virtual screening.
 
Human kallikrein 6 inhibitors with a para-amidobenzylanmine P1 group identified through virtual screening.,Liang G, Chen X, Aldous S, Pu SF, Mehdi S, Powers E, Xia T, Wang R Bioorg Med Chem Lett. 2012 Apr 1;22(7):2450-5. Epub 2012 Feb 14. PMID:22386244<ref>PMID:22386244</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3vfe" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Chen, X]]
[[Category: Chen X]]
[[Category: Wang, R]]
[[Category: Wang R]]
[[Category: Xia, T]]
[[Category: Xia T]]
[[Category: Zhang, Y]]
[[Category: Zhang Y]]
[[Category: Amidinothiophene]]
[[Category: Hk6]]
[[Category: Human kallikrein 6]]
[[Category: Hydrolase]]
[[Category: Protein-ligand complex]]
[[Category: Serine protease]]

Revision as of 14:27, 14 March 2024

Virtual Screening and X-Ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 Group

3vfe, resolution 1.88Å

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