6har - Revision history

OCA at 10:26, 18 March 2021

2021-03-18T10:26:27Z

←Older revision		Revision as of 10:26, 18 March 2021
Line 3:		Line 3:
	<StructureSection load='6har' size='340' side='right'caption='[[6har]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='6har' size='340' side='right'caption='[[6har]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6har]] 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=6HAR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6HAR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6har]] 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=6HAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HAR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRSS3 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), APP ([~~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">PRSS3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), APP ([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=6har FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6har OCA], [~~http~~://pdbe.org/6har PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6har RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6har PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6har 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=6har FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6har OCA], [https://pdbe.org/6har PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6har RCSB], [https://www.ebi.ac.uk/pdbsum/6har PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6har ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 07:49, 10 April 2019

2019-04-10T07:49:33Z

←Older revision		Revision as of 07:49, 10 April 2019
Line 1:		Line 1:

	==Crystal structure of Mesotrypsin in complex with APPI-M17C/I18F/F34C==		==Crystal structure of Mesotrypsin in complex with APPI-M17C/I18F/F34C==
-	<StructureSection load='6har' size='340' side='right' caption='[[6har]], [[Resolution\|resolution]] 1.50Å' scene=''>	+	<StructureSection load='6har' size='340' side='right'caption='[[6har]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6har]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HAR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HAR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6har]] 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=6HAR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HAR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRSS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), APP ([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=6har FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6har OCA], [http://pdbe.org/6har PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6har RCSB], [http://www.ebi.ac.uk/pdbsum/6har PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6har 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=6har FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6har OCA], [http://pdbe.org/6har PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6har RCSB], [http://www.ebi.ac.uk/pdbsum/6har PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6har ProSAT]</span></td></tr>
	</table>		</table>
Line 20:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Cohen, I]]		[[Category: Cohen, I]]
	[[Category: Papo, N]]		[[Category: Papo, N]]

OCA at 09:50, 13 February 2019

2019-02-13T09:50:34Z

←Older revision		Revision as of 09:50, 13 February 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6har is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of Mesotrypsin in complex with APPI-M17C/I18F/F34C==
		+	<StructureSection load='6har' size='340' side='right' caption='[[6har]], [[Resolution\|resolution]] 1.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6har]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HAR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HAR FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6har FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6har OCA], [http://pdbe.org/6har PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6har RCSB], [http://www.ebi.ac.uk/pdbsum/6har PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6har ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Serine protease inhibitors of the Kunitz-bovine pancreatic trypsin inhibitor (BPTI) family are ubiquitous biological regulators of proteolysis. These small proteins are resistant to proteolysis, but can be slowly cleaved within the protease binding loop by target proteases, thereby compromising their activity. For the human protease, mesotrypsin, this cleavage is especially rapid. Here, we aimed to stabilize the Kunitz domain structure against proteolysis through disulfide engineering. Substitution within the Kunitz inhibitor domain of the amyloid precursor protein (APPI) that incorporated a new disulfide bond between residues 17 and 34 reduced proteolysis by mesotrypsin 54-fold. Similar disulfide engineering of tissue factor pathway inhibitor-1 Kunitz domain 1 (KD1TFPI1) and bikunin Kunitz domain 2 (KD2bikunin) likewise stabilized these inhibitors against mesotrypsin proteolysis 17-fold and 6.6-fold, respectively. Crystal structures of disulfide-engineered APPI and KD1TFPI1 variants in a complex with mesotrypsin at 1.5 A and 2.0 A resolution, respectively, confirmed the formation of well-ordered disulfide bonds positioned to stabilize the binding loop. Long all-atom molecular dynamics simulations of disulfide-engineered Kunitz domains and their complexes with mesotrypsin revealed conformational stabilization of the primed side of the inhibitor binding loop by the engineered disulfide, along with global suppression of conformational dynamics in the Kunitz domain. Our findings suggest that the Cys17-Cys34 disulfide slows proteolysis by dampening conformational fluctuations in the binding loop and minimizing motion at the enzyme-inhibitor interface. The generalizable approach developed here for the stabilization against proteolysis of Kunitz domains, which can serve as important scaffolds for therapeutics, may thus find applications in drug development.

-	~~Authors:~~ Shahar, A., ~~Cohen~~, I., Radisky~~, E.~~, Papo, N.	+	Disulfide engineering of human Kunitz-type serine protease inhibitors enhances proteolytic stability and target affinity toward mesotrypsin.,Cohen I, Coban M, Shahar A, Sankaran B, Hockla A, Lacham S, Caulfield TR, Radisky ES, Papo N J Biol Chem. 2019 Jan 30. pii: RA118.007292. doi: 10.1074/jbc.RA118.007292. PMID:30700553<ref>PMID:30700553</ref>

-	~~Description: Crystal structure~~ of ~~Mesotrypsin in complex with APPI-M17C~~/~~I18F/F34C~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	~~[[Category: Shahar, A]]~~	+	<div class="pdbe-citations 6har" style="background-color:#fffaf0;"></div>
-	~~[[Category: Radisky, E]]~~	+	== References ==
-	~~[[Category: Papo, N]]~~	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Cohen, I]]		[[Category: Cohen, I]]
		+	[[Category: Papo, N]]
		+	[[Category: Radisky, E]]
		+	[[Category: Shahar, A]]
		+	[[Category: Appi]]
		+	[[Category: Kunitz type inhibitor]]
		+	[[Category: Mesotrypsin]]
		+	[[Category: Protein fibril]]
		+	[[Category: Prss3]]
		+	[[Category: Serine protease]]

OCA at 04:53, 22 August 2018

2018-08-22T04:53:45Z

←Older revision		Revision as of 04:53, 22 August 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6har is ON HOLD	+	The entry 6har is ON HOLD until Paper Publication

	Authors: Shahar, A., Cohen, I., Radisky, E., Papo, N.		Authors: Shahar, A., Cohen, I., Radisky, E., Papo, N.

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

2018-08-15T15:03:54Z

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

←Older revision

Revision as of 15:03, 15 August 2018

OCA: New page: '''Unreleased structure''' The entry 6har is ON HOLD Authors: Shahar, A., Cohen, I., Radisky, E., Papo, N. Description: Crystal structure of Mesotrypsin in complex with APPI-M17C/I18F/...

2018-08-15T15:03:52Z

New page: '''Unreleased structure''' The entry 6har is ON HOLD Authors: Shahar, A., Cohen, I., Radisky, E., Papo, N. Description: Crystal structure of Mesotrypsin in complex with APPI-M17C/I18F/...

New page

'''Unreleased structure'''

The entry 6har is ON HOLD

Authors: Shahar, A., Cohen, I., Radisky, E., Papo, N.

Description: Crystal structure of Mesotrypsin in complex with APPI-M17C/I18F/F34C
[[Category: Unreleased Structures]]
[[Category: Shahar, A]]
[[Category: Radisky, E]]
[[Category: Papo, N]]
[[Category: Cohen, I]]