6kbr - Revision history

OCA at 10:29, 22 November 2023

OCA — Wed, 22 Nov 2023 10:29:28 GMT

←Older revision		Revision as of 10:29, 22 November 2023
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	<StructureSection load='6kbr' size='340' side='right'caption='[[6kbr]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6kbr' size='340' side='right'caption='[[6kbr]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6kbr]] 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=6KBR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6KBR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6kbr]] is a 2 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=6KBR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KBR 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~~></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~KLK4, EMSP1, PRSS17, PSTS ([http~~:/~~/www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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></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=6kbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kbr OCA], [~~http~~://pdbe.org/6kbr PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6kbr RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6kbr PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6kbr 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=6kbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kbr OCA], [https://pdbe.org/6kbr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kbr RCSB], [https://www.ebi.ac.uk/pdbsum/6kbr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kbr ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN]] Defects in KLK4 are the cause of amelogenesis imperfecta hypomaturation type 2A1 (AI2A1) [MIM:[~~http~~://omim.org/entry/204700 204700]]. AI2A1 is an autosomal recessive defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel.<ref>PMID:15235027</ref>	+	[https://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN] Defects in KLK4 are the cause of amelogenesis imperfecta hypomaturation type 2A1 (AI2A1) [MIM:[https://omim.org/entry/204700 204700]. AI2A1 is an autosomal recessive defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel.<ref>PMID:15235027</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN]] Involved in enamel formation.<ref>PMID:15235027</ref>	+	[https://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN] Involved in enamel formation.<ref>PMID:15235027</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 6kbr" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6kbr" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Kallikrein 3D structures\|Kallikrein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kawaguchi, Y]]	+	[[Category: Kawaguchi Y]]
-	[[Category: Nishimiya, D]]	+	[[Category: Nishimiya D]]
-	~~[[Category: Cystine knot protein]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Protease inhibitor]]~~	+
-	~~[[Category: Protein binding]]~~	+
-	~~[[Category: Protein engineering]]~~	+
-	~~[[Category: Structural analysis~~]]	+

OCA at 06:35, 21 August 2019

OCA — Wed, 21 Aug 2019 06:35:25 GMT

←Older revision		Revision as of 06:35, 21 August 2019
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	<StructureSection load='6kbr' size='340' side='right'caption='[[6kbr]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6kbr' size='340' side='right'caption='[[6kbr]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6kbr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KBR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KBR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6kbr]] 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=6KBR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KBR 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></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KLK4, EMSP1, PRSS17, PSTS ([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=6kbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kbr OCA], [http://pdbe.org/6kbr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kbr RCSB], [http://www.ebi.ac.uk/pdbsum/6kbr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kbr ProSAT]</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=6kbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kbr OCA], [http://pdbe.org/6kbr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kbr RCSB], [http://www.ebi.ac.uk/pdbsum/6kbr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kbr ProSAT]</span></td></tr>
	</table>		</table>
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	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN]] Involved in enamel formation.<ref>PMID:15235027</ref>		[[http://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN]] Involved in enamel formation.<ref>PMID:15235027</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Proteases are one of attractive therapeutic targets to play key roles in pharmacological action. There are many protease inhibitors in nature, and most of them structurally have cystine knot motifs. Their structures are favorable for recognition of active pockets of proteases, leading to the potent inhibition. However, they also have drawbacks, such as broad cross-reactivity, on the therapeutic application. To create therapeutic proteins derived from a disulfide-rich scaffold, we selected human serine protease inhibitor Kazal type 2 (SPINK2) through a scaffold screening, as a protein scaffold with requirements for therapeutic proteins. We then constructed a diverse library of the engineered SPINK2 by introducing random mutations into its flexible loop region with the designed method. By phage panning against four serine proteases, we isolated potent inhibitors against each target with picomolar KD and sub-nanomolar Ki values. Also, they exhibited the desired specificities against target proteases without inhibiting non-target proteases. The crystal structure of kallikrein related peptidase 4 (KLK4)-engineered SPINK2 complex revealed the interface with extensive conformational complementarity. Our study demonstrates that engineered SPINK2 can serve as a scaffold to generate therapeutic molecules against target proteins with groove structures.
		+
		+	A protein scaffold, engineered SPINK2, for generation of inhibitors with high affinity and specificity against target proteases.,Nishimiya D, Kawaguchi Y, Kodama S, Nasu H, Yano H, Yamaguchi A, Tamura M, Hashimoto R Sci Rep. 2019 Aug 7;9(1):11436. doi: 10.1038/s41598-019-47615-5. PMID:31391482<ref>PMID:31391482</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6kbr" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Kawaguchi, Y]]		[[Category: Kawaguchi, Y]]

OCA at 10:43, 17 July 2019

OCA — Wed, 17 Jul 2019 10:43:59 GMT

←Older revision		Revision as of 10:43, 17 July 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6kbr is ~~ON HOLD~~	+	==Crystal structure of Human KLK4 and SPINK2 derived KLK4 inhibitor complex==
-		+	<StructureSection load='6kbr' size='340' side='right'caption='[[6kbr]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~Authors~~: ~~Kawaguchi~~, Y., ~~Nishimiya~~, D.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6kbr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KBR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KBR FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of Human~~ KLK4 and ~~SPINK2 derived KLK4 inhibitor complex~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6kbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kbr OCA], [http://pdbe.org/6kbr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kbr RCSB], [http://www.ebi.ac.uk/pdbsum/6kbr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kbr ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN]] Defects in KLK4 are the cause of amelogenesis imperfecta hypomaturation type 2A1 (AI2A1) [MIM:[http://omim.org/entry/204700 204700]]. AI2A1 is an autosomal recessive defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel.<ref>PMID:15235027</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN]] Involved in enamel formation.<ref>PMID:15235027</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Kawaguchi, Y]]		[[Category: Kawaguchi, Y]]
	[[Category: Nishimiya, D]]		[[Category: Nishimiya, D]]
		+	[[Category: Cystine knot protein]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Protease inhibitor]]
		+	[[Category: Protein binding]]
		+	[[Category: Protein engineering]]
		+	[[Category: Structural analysis]]

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

OCA — Wed, 03 Jul 2019 04:07:17 GMT

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

←Older revision

Revision as of 04:07, 3 July 2019

OCA: New page: '''Unreleased structure''' The entry 6kbr is ON HOLD Authors: Kawaguchi, Y., Nishimiya, D. Description: Crystal structure of Human KLK4 and SPINK2 derived KLK4 inhibitor complex [[Cate...

OCA — Wed, 03 Jul 2019 04:07:16 GMT

New page: '''Unreleased structure''' The entry 6kbr is ON HOLD Authors: Kawaguchi, Y., Nishimiya, D. Description: Crystal structure of Human KLK4 and SPINK2 derived KLK4 inhibitor complex [[Cate...

New page

'''Unreleased structure'''

The entry 6kbr is ON HOLD

Authors: Kawaguchi, Y., Nishimiya, D.

Description: Crystal structure of Human KLK4 and SPINK2 derived KLK4 inhibitor complex
[[Category: Unreleased Structures]]
[[Category: Kawaguchi, Y]]
[[Category: Nishimiya, D]]