View source for 3vfe


==Virtual Screening and X-Ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 Group==
<StructureSection load='3vfe' size='340' side='right'caption='[[3vfe]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
<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='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='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>
</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 ==
A series of compounds with an amidinothiophene P1 group and a pyrrolidinone-sulphonamide scaffold linker was identified as potent inhibitors of human kallikrein 6 by structure-based virtual screening based on the union accessible binding space of serine proteases. As the first series of potent nonmechanism-based hK6 inhibitors, they may be used as tool compounds for target validation. An X-ray structure of a representative compound complexed with hK6, resolved at a resolution of 1.88 A, revealed that the amidinothiophene moiety bound in the S1 pocket and the pyrrolidinone-sulphonamide linker projected the aromatic tail into the S' pocket.

Virtual Screening and X-ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 Group.,Liang G, Chen X, Aldous S, Pu SF, Mehdi S, Powers E, Giovanni A, Kongsamut S, Xia T, Zhang Y, Wang R, Gao Z, Merriman G, McLean LR, Morize I ACS Med Chem Lett. 2012 Jan 11;3(2):159-64. doi: 10.1021/ml200291e. eCollection , 2012 Feb 9. PMID:24900446<ref>PMID:24900446</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==
*[[Kallikrein 3D structures|Kallikrein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen X]]
[[Category: Wang R]]
[[Category: Xia T]]
[[Category: Zhang Y]]