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1l2e

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Revision as of 21:14, 24 January 2018

Human Kallikrein 6 (hK6) Active Form with benzamidine inhibitor

Structural highlights

1l2e is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

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

The human kallikreins are a large multigene family of closely related serine-type proteases. In this regard, they are similar to the multigene kallikrein families characterized in mice and rats. There is a much more extensive body of knowledge regarding the function of mouse and rat kallikreins in comparison with the human kallikreins. Human kallikrein 6 has been proposed as the homologue to rat myelencephalon-specific protease, an arginine-specific degradative-type protease abundantly expressed in the central nervous system and implicated in demyelinating disease. We present the x-ray crystal structure of mature, active recombinant human kallikrein 6 at 1.75-A resolution. This high resolution model provides the first three-dimensional view of one of the human kallikreins and one of only a few structures of serine proteases predominantly expressed in the central nervous system. Enzymatic data are presented that support the identification of human kallikrein 6 as the functional homologue of rat myelencephalon-specific protease and are corroborated by a molecular phylogenetic analysis. Furthermore, the x-ray data provide support for the characterization of human kallikrein 6 as a degradative protease with structural features more similar to trypsin than the regulatory kallikreins.

Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system.,Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, Blaber M J Biol Chem. 2002 Jul 5;277(27):24562-70. Epub 2002 Apr 30. PMID:11983703^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Magklara A, Mellati AA, Wasney GA, Little SP, Sotiropoulou G, Becker GW, Diamandis EP. Characterization of the enzymatic activity of human kallikrein 6: Autoactivation, substrate specificity, and regulation by inhibitors. Biochem Biophys Res Commun. 2003 Aug 8;307(4):948-55. PMID:12878203
↑ Iwata A, Maruyama M, Akagi T, Hashikawa T, Kanazawa I, Tsuji S, Nukina N. Alpha-synuclein degradation by serine protease neurosin: implication for pathogenesis of synucleinopathies. Hum Mol Genet. 2003 Oct 15;12(20):2625-35. Epub 2003 Aug 19. PMID:12928483 doi:http://dx.doi.org/10.1093/hmg/ddg283
↑ Ghosh MC, Grass L, Soosaipillai A, Sotiropoulou G, Diamandis EP. Human kallikrein 6 degrades extracellular matrix proteins and may enhance the metastatic potential of tumour cells. Tumour Biol. 2004 Jul-Aug;25(4):193-9. PMID:15557757 doi:http://dx.doi.org/10.1159/000081102
↑ Scarisbrick IA, Sabharwal P, Cruz H, Larsen N, Vandell AG, Blaber SI, Ameenuddin S, Papke LM, Fehlings MG, Reeves RK, Blaber M, Windebank AJ, Rodriguez M. Dynamic role of kallikrein 6 in traumatic spinal cord injury. Eur J Neurosci. 2006 Sep;24(5):1457-69. PMID:16987227 doi:http://dx.doi.org/10.1111/j.1460-9568.2006.05021.x
↑ Angelo PF, Lima AR, Alves FM, Blaber SI, Scarisbrick IA, Blaber M, Juliano L, Juliano MA. Substrate specificity of human kallikrein 6: salt and glycosaminoglycan activation effects. J Biol Chem. 2006 Feb 10;281(6):3116-26. Epub 2005 Dec 1. PMID:16321973 doi:http://dx.doi.org/M510096200
↑ Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, Blaber M. Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system. J Biol Chem. 2002 Jul 5;277(27):24562-70. Epub 2002 Apr 30. PMID:11983703 doi:10.1074/jbc.M202392200
↑ Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, Blaber M. Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system. J Biol Chem. 2002 Jul 5;277(27):24562-70. Epub 2002 Apr 30. PMID:11983703 doi:10.1074/jbc.M202392200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1l2e"

@@ Line 1: / Line 1: @@
 ==Human Kallikrein 6 (hK6) Active Form with benzamidine inhibitor==
 <StructureSection load='1l2e' size='340' side='right' caption='[[1l2e]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[1l2e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L2E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1L2E FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=1l2e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l2e OCA], [http://pdbe.org/1l2e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l2e RCSB], [http://www.ebi.ac.uk/pdbsum/1l2e PDBsum]</span></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=1l2e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l2e OCA], [http://pdbe.org/1l2e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l2e RCSB], [http://www.ebi.ac.uk/pdbsum/1l2e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1l2e ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 12: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l2/1l2e_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l2/1l2e_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 27: / Line 28: @@
 </div>
 <div class="pdbe-citations 1l2e" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Kallikrein|Kallikrein]]
 == References ==
 <references/>

1l2e

From Proteopedia

Revision as of 21:14, 24 January 2018

Human Kallikrein 6 (hK6) Active Form with benzamidine inhibitor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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