1lo6: Difference between revisions

Latest revision as of 06:58, 30 October 2024

Human Kallikrein 6 (hK6) active form with benzamidine inhibitor at 1.56 A resolution

Structural highlights

1lo6 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.56Å
Ligands:	BEN, MG
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.

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:https://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:https://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:https://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:https://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

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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:https://dx.doi.org/10.1093/hmg/ddg283

[3] 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:https://dx.doi.org/10.1159/000081102

[4] 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:https://dx.doi.org/10.1111/j.1460-9568.2006.05021.x

[5] 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:https://dx.doi.org/M510096200

[6] 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

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@@ Line 1: / Line 1: @@
-[[Image:1lo6.gif|left|200px]]<br />
-<applet load="1lo6" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1lo6, resolution 1.56&Aring;" />
-'''Human Kallikrein 6 (hK6) active form with benzamidine inhibitor at 1.56 A resolution'''<br />
-==About this Structure==
+==Human Kallikrein 6 (hK6) active form with benzamidine inhibitor at 1.56 A resolution==
-LO6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and BEN as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LO6 OCA].
+<StructureSection load='1lo6' size='340' side='right'caption='[[1lo6]], [[Resolution|resolution]] 1.56&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1lo6]] 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=1LO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LO6 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]] 1.56&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=1lo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lo6 OCA], [https://pdbe.org/1lo6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lo6 RCSB], [https://www.ebi.ac.uk/pdbsum/1lo6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lo6 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>
+== 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/lo/1lo6_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=1lo6 ConSurf].
+<div style="clear:both"></div>
+==See Also==
+*[[Kallikrein 3D structures|Kallikrein 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Bernett, M.J.]]
+[[Category: Bernett MJ]]
-[[Category: Blaber, M.]]
+[[Category: Blaber M]]
-[[Category: Blaber, S.I.]]
+[[Category: Blaber SI]]
-[[Category: Dhanarajan, P.]]
+[[Category: Dhanarajan P]]
-[[Category: Scarisbrick, I.A.]]
+[[Category: Scarisbrick IA]]
-[[Category: Thompson, S.M.]]
+[[Category: Thompson SM]]
-[[Category: BEN]]
-[[Category: MG]]
-[[Category: benzamidine]]
-[[Category: brain serine protease]]
-[[Category: hk6]]
-[[Category: human kallikrein 6]]
-[[Category: kallikrein]]
-[[Category: msp]]
-[[Category: myelencephalon specific protease]]
-[[Category: neurosin]]
-[[Category: protease]]
-[[Category: protease m]]
-[[Category: serine protease]]
-[[Category: zyme]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:02:52 2007''

1lo6: Difference between revisions

Latest revision as of 06:58, 30 October 2024

Human Kallikrein 6 (hK6) active form with benzamidine inhibitor at 1.56 A resolution

Structural highlights

Function

Evolutionary Conservation

See Also

References

Contents

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