6p0p - Revision history

OCA at 07:20, 11 October 2023

OCA — Wed, 11 Oct 2023 07:20:45 GMT

←Older revision		Revision as of 07:20, 11 October 2023
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	<StructureSection load='6p0p' size='340' side='right'caption='[[6p0p]], [[Resolution\|resolution]] 2.55Å' scene=''>		<StructureSection load='6p0p' size='340' side='right'caption='[[6p0p]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6p0p]] 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=6P0P OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6P0P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6p0p]] 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=6P0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P0P FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=Y35:(3-{4-[3-(aminomethyl)phenyl]piperidine-1-carbonyl}[1,1-biphenyl]-3-yl){4-[3-(aminomethyl)phenyl]piperidin-1-yl}[3,4-di(hydroxy-kappaO)phenyl]methanonato(2-)hydroxyborate(1-)'>Y35</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]] 2.55Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TPSAB1, TPS1, TPS2, TPSB1 ([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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=Y35:(3-{4-[3-(aminomethyl)phenyl]piperidine-1-carbonyl}[1,1-biphenyl]-3-yl){4-[3-(aminomethyl)phenyl]piperidin-1-yl}[3,4-di(hydroxy-kappaO)phenyl]methanonato(2-)hydroxyborate(1-)'>Y35</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tryptase Tryptase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.59 3.4.21.59] </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=6p0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p0p OCA], [https://pdbe.org/6p0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p0p RCSB], [https://www.ebi.ac.uk/pdbsum/6p0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p0p ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6p0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p0p OCA], [~~http~~://pdbe.org/6p0p PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6p0p RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6p0p PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6p0p ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TRYB1_HUMAN TRYB1_HUMAN]] Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type (By similarity).	+	[https://www.uniprot.org/uniprot/TRYB1_HUMAN TRYB1_HUMAN] Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6p0p" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6p0p" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tryptase\|Tryptase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Tryptase]]~~	+	[[Category: Arnold LD]]
-	[[Category: Arnold~~, L D~~]]	+	[[Category: Barany F]]
-	[[Category: Barany, F]]	+	[[Category: Bergstrom DE]]
-	[[Category: Bergstrom~~, D E~~]]	+	[[Category: Feinberg PB]]
-	[[Category: Feinberg~~, P B~~]]	+	[[Category: Foreman KW]]
-	[[Category: Foreman~~, K W~~]]	+	[[Category: Giardina SF]]
-	[[Category: Giardina~~, S F~~]]	+	[[Category: Pingle MR]]
-	[[Category: Pingle~~, M R~~]]	+	[[Category: Werner DS]]
-	[[Category: Werner~~, D S]]~~	+
-	~~[[Category: Bivalent inhibitor]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Protease inhibitor~~]]	+

OCA at 07:19, 8 April 2020

OCA — Wed, 08 Apr 2020 07:19:56 GMT

←Older revision		Revision as of 07:19, 8 April 2020
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	<StructureSection load='6p0p' size='340' side='right'caption='[[6p0p]], [[Resolution\|resolution]] 2.55Å' scene=''>		<StructureSection load='6p0p' size='340' side='right'caption='[[6p0p]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6p0p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P0P OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6P0P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6p0p]] 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=6P0P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6P0P FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=Y35:(3-{4-[3-(aminomethyl)phenyl]piperidine-1-carbonyl}[1,1-biphenyl]-3-yl){4-[3-(aminomethyl)phenyl]piperidin-1-yl}[3,4-di(hydroxy-kappaO)phenyl]methanonato(2-)hydroxyborate(1-)'>Y35</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=Y35:(3-{4-[3-(aminomethyl)phenyl]piperidine-1-carbonyl}[1,1-biphenyl]-3-yl){4-[3-(aminomethyl)phenyl]piperidin-1-yl}[3,4-di(hydroxy-kappaO)phenyl]methanonato(2-)hydroxyborate(1-)'>Y35</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TPSAB1, TPS1, TPS2, TPSB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tryptase Tryptase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.59 3.4.21.59] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tryptase Tryptase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.59 3.4.21.59] </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=6p0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p0p OCA], [http://pdbe.org/6p0p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p0p RCSB], [http://www.ebi.ac.uk/pdbsum/6p0p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p0p ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6p0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p0p OCA], [http://pdbe.org/6p0p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p0p RCSB], [http://www.ebi.ac.uk/pdbsum/6p0p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p0p ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Tryptase]]		[[Category: Tryptase]]

OCA at 10:11, 27 March 2020

OCA — Fri, 27 Mar 2020 10:11:17 GMT

←Older revision		Revision as of 10:11, 27 March 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6p0p is ~~ON HOLD until Paper~~ Publication	+	==Human beta-tryptase co-crystal structure with 5-{4-[3-(aminomethyl)phenyl]piperidine-1-carbonyl}-2-(3'-{4-[3-(aminomethyl)phenyl]piperidine-1-carbonyl}-[1,1'-biphenyl]-3-yl)-2-hydroxy-2H-1,3,2-benzodioxaborol-2-uide==
		+	<StructureSection load='6p0p' size='340' side='right'caption='[[6p0p]], [[Resolution\|resolution]] 2.55Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6p0p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P0P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P0P FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=Y35:(3-{4-[3-(aminomethyl)phenyl]piperidine-1-carbonyl}[1,1-biphenyl]-3-yl){4-[3-(aminomethyl)phenyl]piperidin-1-yl}[3,4-di(hydroxy-kappaO)phenyl]methanonato(2-)hydroxyborate(1-)'>Y35</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tryptase Tryptase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.59 3.4.21.59] </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=6p0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p0p OCA], [http://pdbe.org/6p0p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p0p RCSB], [http://www.ebi.ac.uk/pdbsum/6p0p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p0p ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TRYB1_HUMAN TRYB1_HUMAN]] Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	beta-Tryptase, a homotetrameric serine protease, has four identical active sites facing a central pore, presenting an optimized setting for the rational design of bivalent inhibitors that bridge two adjacent sites. Using diol, hydroxymethyl phenols or benzoyl methyl hydroxamates, and boronic acid chemistries to reversibly join two [3-(1-acylpiperidin-4-yl)phenyl]methanamine core ligands, we have successfully produced a series of self-assembling heterodimeric inhibitors. These heterodimeric tryptase inhibitors demonstrate superior activity compared to monomeric modes of inhibition. X-ray crystallography validated the dimeric mechanism of inhibition, and compounds demonstrated high selectivity against related proteases, good target engagement, and tryptase inhibition in HMC1 xenograft models. Screening 3872 possible combinations from 44 boronic acid and 88 diol derivatives revealed several combinations that produced nanomolar inhibition, and seven unique pairs produced greater than 100-fold improvement in potency over monomeric inhibition. These heterodimeric tryptase inhibitors demonstrate the power of target-driven combinatorial chemistry to deliver bivalent drugs in a small molecule form.

-	~~Authors~~:	+	Novel, Self-Assembling Dimeric Inhibitors of Human beta Tryptase.,Giardina SF, Werner DS, Pingle M, Feinberg PB, Foreman KW, Bergstrom DE, Arnold LD, Barany F J Med Chem. 2020 Feb 27. doi: 10.1021/acs.jmedchem.9b01689. PMID:32057241<ref>PMID:32057241</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6p0p" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Tryptase]]
		+	[[Category: Arnold, L D]]
		+	[[Category: Barany, F]]
		+	[[Category: Bergstrom, D E]]
		+	[[Category: Feinberg, P B]]
		+	[[Category: Foreman, K W]]
		+	[[Category: Giardina, S F]]
		+	[[Category: Pingle, M R]]
		+	[[Category: Werner, D S]]
		+	[[Category: Bivalent inhibitor]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Protease inhibitor]]

OCA at 08:53, 17 July 2019

OCA — Wed, 17 Jul 2019 08:53:17 GMT

←Older revision		Revision as of 08:53, 17 July 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6p0p is ON HOLD	+	The entry 6p0p is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6p0p" [edit=sysop:move=sysop]

OCA — Wed, 29 May 2019 04:33:42 GMT

Protected "6p0p" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:33, 29 May 2019

OCA: New page: '''Unreleased structure''' The entry 6p0p is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 29 May 2019 04:33:40 GMT

New page: '''Unreleased structure''' The entry 6p0p is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6p0p is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]