View source for 1gvl

==HUMAN PROKALLIKREIN 6 (HK6)/ PROZYME/ PROPROTEASE M/ PRONEUROSIN==
<StructureSection load='1gvl' size='340' side='right' caption='[[1gvl]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1gvl]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GVL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1GVL FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gvl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gvl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1gvl RCSB], [http://www.ebi.ac.uk/pdbsum/1gvl PDBsum]</span></td></tr>
</table>
== Function ==
[[http://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>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gv/1gvl_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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== Publication Abstract from PubMed ==
Zyme/protease M/neurosin/human kallikrein 6 (hK6) is a member of the human kallikrein family of trypsin-like serine proteinases and was originally identified as being down-regulated in metastatic breast and ovarian tumors when compared with corresponding primary tumors. Recent evidence suggests that hK6 may serve as a circulating tumor marker in ovarian cancers. In addition, it was described in the brain of Parkinson's disease and Alzheimer's disease patients, where it is implicated in amyloid precursor protein processing. It is thus a biomarker for these diseases. To examine the mechanism of activation of hK6, we have solved the structure of its proform, the first of a human kallikrein family member. The proenzyme displays a fold that exhibits chimeric features between those of trypsinogen and other family members. It lacks the characteristic "kallikrein loop" and forms the six disulfide bridges of trypsin. Pro-hK6 displays a completely closed specificity pocket and a unique conformation of the regions involved in structural rearrangements upon proteolytic cleavage activation. This points to a novel activation mechanism, which could be extrapolated to other human kallikreins.

The structure of human prokallikrein 6 reveals a novel activation mechanism for the kallikrein family.,Gomis-Ruth FX, Bayes A, Sotiropoulou G, Pampalakis G, Tsetsenis T, Villegas V, Aviles FX, Coll M J Biol Chem. 2002 Jul 26;277(30):27273-81. Epub 2002 May 16. PMID:12016211<ref>PMID:12016211</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Aviles, F X]]
[[Category: Bayes, A]]
[[Category: Coll, M]]
[[Category: Gomis-Ruth, F X]]
[[Category: Pampalakis, G]]
[[Category: Sotiropoulou, G]]
[[Category: Tsetsenis, T]]
[[Category: Villegas, V]]
[[Category: Human kallikrein]]
[[Category: Hydrolase]]
[[Category: Zymogen]]