7arg - Revision history

OCA at 12:14, 1 February 2024

2024-02-01T12:14:51Z

←Older revision		Revision as of 12:14, 1 February 2024
Line 3:		Line 3:
	<StructureSection load='7arg' size='340' side='right'caption='[[7arg]], [[Resolution\|resolution]] 1.24Å' scene=''>		<StructureSection load='7arg' size='340' side='right'caption='[[7arg]], [[Resolution\|resolution]] 1.24Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7arg]] is a 1 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=7ARG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ARG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7arg]] 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=7ARG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ARG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RW8:methyl+4-(2,3-dihydroindol-1-yl)-4-oxidanylidene-butanoate'>RW8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.24Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NOTUM, OK/SW-CL.30 ([https://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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RW8:methyl+4-(2,3-dihydroindol-1-yl)-4-oxidanylidene-butanoate'>RW8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/[Wnt_protein]_O-palmitoleoyl-L-serine_hydrolase [Wnt protein] O-palmitoleoyl-L-serine hydrolase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.98 3.1.1.98] </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=7arg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7arg OCA], [https://pdbe.org/7arg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7arg RCSB], [https://www.ebi.ac.uk/pdbsum/7arg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7arg 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=7arg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7arg OCA], [https://pdbe.org/7arg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7arg RCSB], [https://www.ebi.ac.uk/pdbsum/7arg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7arg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/NOTUM_HUMAN NOTUM_HUMAN]] May deacetylate GlcNAc residues on cell surface glycans.	+	[https://www.uniprot.org/uniprot/NOTUM_HUMAN NOTUM_HUMAN] May deacetylate GlcNAc residues on cell surface glycans.
	<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 7arg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7arg" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Carboxylesterase 3D structures\|Carboxylesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Jones~~, E Y~~]]	+	[[Category: Jones EY]]
-	[[Category: Zhao, Y]]	+	[[Category: Zhao Y]]
-	~~[[Category: Notum inhibitor]]~~	+
-	~~[[Category: Signaling protein~~]]	+

OCA at 06:28, 25 August 2021

2021-08-25T06:28:58Z

←Older revision		Revision as of 06:28, 25 August 2021
Line 1:		Line 1:

	==Notum in complex with ARUK3002704==		==Notum in complex with ARUK3002704==
-	<StructureSection load='7arg' size='340' side='right'caption='[[7arg]]' scene=''>	+	<StructureSection load='7arg' size='340' side='right'caption='[[7arg]], [[Resolution\|resolution]] 1.24Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ARG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ARG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7arg]] is a 1 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=7ARG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ARG FirstGlance]. <br>
-	</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=7arg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7arg OCA], [https://pdbe.org/7arg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7arg RCSB], [https://www.ebi.ac.uk/pdbsum/7arg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7arg ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RW8:methyl+4-(2,3-dihydroindol-1-yl)-4-oxidanylidene-butanoate'>RW8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NOTUM, OK/SW-CL.30 ([https://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'>[https://en.wikipedia.org/wiki/[Wnt_protein]_O-palmitoleoyl-L-serine_hydrolase [Wnt protein] O-palmitoleoyl-L-serine hydrolase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.98 3.1.1.98] </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=7arg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7arg OCA], [https://pdbe.org/7arg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7arg RCSB], [https://www.ebi.ac.uk/pdbsum/7arg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7arg ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/NOTUM_HUMAN NOTUM_HUMAN]] May deacetylate GlcNAc residues on cell surface glycans.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The carboxylesterase Notum hydrolyzes a palmitoleate moiety from Wingless/Integrated(Wnt) ligands and deactivates Wnt signaling. Notum inhibitors can restore Wnt signaling which may be of therapeutic benefit for pathologies such as osteoporosis and Alzheimer's disease. We report the identification of a novel class of covalent Notum inhibitors, 4-(indolin-1-yl)-4-oxobutanoate esters. High-resolution crystal structures of the Notum inhibitor complexes reveal a common covalent adduct formed between the nucleophile serine-232 and hydrolyzed butyric esters. The covalent interaction in solution was confirmed by mass spectrometry analysis. Inhibitory potencies vary depending on the warheads used. Mechanistically, the resulting acyl-enzyme intermediate carbonyl atom is positioned at an unfavorable angle for the approach of the active site water, which, combined with strong hydrophobic interactions with the enzyme pocket residues, hinders the intermediate from being further processed and results in covalent inhibition. These insights into Notum catalytic inhibition may guide development of more potent Notum inhibitors.
		+
		+	Structural Insights into Notum Covalent Inhibition.,Zhao Y, Svensson F, Steadman D, Frew S, Monaghan A, Bictash M, Moreira T, Chalk R, Lu W, Fish PV, Jones EY J Med Chem. 2021 Jul 22. doi: 10.1021/acs.jmedchem.1c00701. PMID:34292747<ref>PMID:34292747</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7arg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Jones EY]]	+	[[Category: Jones, E Y]]
-	[[Category: Zhao Y]]	+	[[Category: Zhao, Y]]
		+	[[Category: Notum inhibitor]]
		+	[[Category: Signaling protein]]

OCA at 10:16, 4 August 2021

2021-08-04T10:16:43Z

←Older revision		Revision as of 10:16, 4 August 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7arg ~~is ON HOLD until Paper Publication~~	+	==Notum in complex with ARUK3002704==
-		+	<StructureSection load='7arg' size='340' side='right'caption='[[7arg]]' scene=''>
-	~~Authors~~: ~~Zhao~~, Y., ~~Jones~~, E.Y.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ARG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ARG FirstGlance]. <br>
-	~~Description: Notum in complex with ARUK3002704~~	+	</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=7arg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7arg OCA], [https://pdbe.org/7arg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7arg RCSB], [https://www.ebi.ac.uk/pdbsum/7arg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7arg ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Zhao, Y~~]]	+	__TOC__
-	[[Category: ~~Jones, E.~~Y]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Jones EY]]
		+	[[Category: Zhao Y]]

OCA at 05:13, 25 November 2020

2020-11-25T05:13:14Z

←Older revision		Revision as of 05:13, 25 November 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7arg is ON HOLD	+	The entry 7arg is ON HOLD until Paper Publication

	Authors: Zhao, Y., Jones, E.Y.		Authors: Zhao, Y., Jones, E.Y.

OCA: Protected "7arg" [edit=sysop:move=sysop]

2020-11-04T05:20:47Z

Protected "7arg" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:20, 4 November 2020

OCA: New page: '''Unreleased structure''' The entry 7arg is ON HOLD Authors: Zhao, Y., Jones, E.Y. Description: Notum in complex with ARUK3002704 Category: Unreleased Structures [[Category: Zhao,...

2020-11-04T05:20:46Z

New page: '''Unreleased structure''' The entry 7arg is ON HOLD Authors: Zhao, Y., Jones, E.Y. Description: Notum in complex with ARUK3002704 Category: Unreleased Structures [[Category: Zhao,...

New page

'''Unreleased structure'''

The entry 7arg is ON HOLD

Authors: Zhao, Y., Jones, E.Y.

Description: Notum in complex with ARUK3002704
[[Category: Unreleased Structures]]
[[Category: Zhao, Y]]
[[Category: Jones, E.Y]]