6qh9 - Revision history

OCA at 10:38, 18 March 2021

OCA — Thu, 18 Mar 2021 10:38:36 GMT

←Older revision		Revision as of 10:38, 18 March 2021
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	==Crystal Structure of Human Kallikrein 6 in complex with GSK3239861A==		==Crystal Structure of Human Kallikrein 6 in complex with GSK3239861A==
-	<StructureSection load='6qh9' size='340' side='right' caption='[[6qh9]], [[Resolution\|resolution]] 2.27Å' scene=''>	+	<StructureSection load='6qh9' size='340' side='right'caption='[[6qh9]], [[Resolution\|resolution]] 2.27Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qh9]] is a 2 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=6QH9 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QH9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qh9]] is a 2 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=6QH9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QH9 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J2N:(3~{S})-~{N}-(4-carbamimidoylphenyl)-2-oxidanylidene-piperidine-3-carboxamide'>J2N</scene>, <scene name='pdbligand=J3B:(3~{R})-~{N}-(4-carbamimidoylphenyl)-2-oxidanylidene-piperidine-3-carboxamide'>J3B</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J2N:(3~{S})-~{N}-(4-carbamimidoylphenyl)-2-oxidanylidene-piperidine-3-carboxamide'>J2N</scene>, <scene name='pdbligand=J3B:(3~{R})-~{N}-(4-carbamimidoylphenyl)-2-oxidanylidene-piperidine-3-carboxamide'>J3B</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KLK6, PRSS18, PRSS9 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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=6qh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qh9 OCA], [~~http~~://pdbe.org/6qh9 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qh9 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qh9 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qh9 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=6qh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qh9 OCA], [https://pdbe.org/6qh9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qh9 RCSB], [https://www.ebi.ac.uk/pdbsum/6qh9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qh9 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== 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>	+	[[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6qh9" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6qh9" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Kallikrein 3D structures\|Kallikrein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Thorpe, J H]]		[[Category: Thorpe, J H]]
	[[Category: Complex]]		[[Category: Complex]]

OCA at 16:09, 27 February 2019

OCA — Wed, 27 Feb 2019 16:09:18 GMT

←Older revision		Revision as of 16:09, 27 February 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6qh9 is ~~ON HOLD~~	+	==Crystal Structure of Human Kallikrein 6 in complex with GSK3239861A==
		+	<StructureSection load='6qh9' size='340' side='right' caption='[[6qh9]], [[Resolution\|resolution]] 2.27Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6qh9]] is a 2 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=6QH9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QH9 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J2N:(3~{S})-~{N}-(4-carbamimidoylphenyl)-2-oxidanylidene-piperidine-3-carboxamide'>J2N</scene>, <scene name='pdbligand=J3B:(3~{R})-~{N}-(4-carbamimidoylphenyl)-2-oxidanylidene-piperidine-3-carboxamide'>J3B</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KLK6, PRSS18, PRSS9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6qh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qh9 OCA], [http://pdbe.org/6qh9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qh9 RCSB], [http://www.ebi.ac.uk/pdbsum/6qh9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qh9 ProSAT]</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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Netherton syndrome (NS) is a rare and debilitating severe autosomal recessive genetic skin disease with high mortality rates particularly in neonates. NS is caused by loss-of-function SPINK5 mutations leading to unregulated kallikrein 5 (KLK5) and kallikrein 7 (KLK7) activity. Furthermore, KLK5 inhibition has been proposed as a potential therapeutic treatment for NS. Identification of potent and selective KLK5 inhibitors would enable further exploration of the disease biology and could ultimately lead to a treatment for NS. This publication describes how fragmentation of known trypsin-like serine protease (TLSP) inhibitors resulted in the identification of a series of phenolic amidine-based KLK5 inhibitors 1. X-ray crystallography was used to find alternatives to the phenol interaction leading to identification of carbonyl analogues such as lactam 13 and benzimidazole 15. These reversible inhibitors, with selectivity over KLK1 (10-100 fold), provided novel starting points for the guided growth towards suitable tool molecules for the exploration of KLK5 biology.

-	~~Authors: Thorpe~~, J.H.	+	Kallikrein 5 inhibitors identified through structure based drug design in search for a treatment for Netherton Syndrome.,White GV, Edgar EV, Holmes DS, Lewell XQ, Liddle J, Polyakova O, Smith KJ, Thorpe JH, Walker AL, Wang Y, Young RJ, Hovnanian A Bioorg Med Chem Lett. 2019 Mar 15;29(6):821-825. doi: 10.1016/j.bmcl.2019.01.020., Epub 2019 Jan 22. PMID:30691925<ref>PMID:30691925</ref>

-	~~Description: Crystal Structure~~ of ~~Human Kallikrein 6 in complex with GSK3239861A~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Thorpe, J.H]]	+	<div class="pdbe-citations 6qh9" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Thorpe, J H]]
		+	[[Category: Complex]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protease]]

OCA: Protected "6qh9" [edit=sysop:move=sysop]

OCA — Wed, 30 Jan 2019 06:57:26 GMT

Protected "6qh9" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:57, 30 January 2019

OCA: New page: '''Unreleased structure''' The entry 6qh9 is ON HOLD Authors: Thorpe, J.H. Description: Crystal Structure of Human Kallikrein 6 in complex with GSK3239861A [[Category: Unreleased Struc...

OCA — Wed, 30 Jan 2019 06:57:24 GMT

New page: '''Unreleased structure''' The entry 6qh9 is ON HOLD Authors: Thorpe, J.H. Description: Crystal Structure of Human Kallikrein 6 in complex with GSK3239861A [[Category: Unreleased Struc...

New page

'''Unreleased structure'''

The entry 6qh9 is ON HOLD

Authors: Thorpe, J.H.

Description: Crystal Structure of Human Kallikrein 6 in complex with GSK3239861A
[[Category: Unreleased Structures]]
[[Category: Thorpe, J.H]]