OCA at 06:36, 27 March 2019

OCA — Wed, 27 Mar 2019 06:36:48 GMT

←Older revision		Revision as of 06:36, 27 March 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6h1a is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of VX surrogate NEMP inhibited recombinant human bile salt activated lipase==
		+	<StructureSection load='6h1a' size='340' side='right'caption='[[6h1a]], [[Resolution\|resolution]] 1.75Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6h1a]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H1A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H1A FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SVX:O-[(R)-ETHOXY(METHYL)PHOSPHORYL]-L-SERINE'>SVX</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=6h1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h1a OCA], [http://pdbe.org/6h1a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h1a RCSB], [http://www.ebi.ac.uk/pdbsum/6h1a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h1a ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CEL_HUMAN CEL_HUMAN]] Defects in CEL are a cause of maturity-onset diabetes of the young type 8 with exocrine dysfunction (MODY8) [MIM:[http://omim.org/entry/609812 609812]]; also known as diabetes and pancreatic exocrine dysfunction (DPED). MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:16369531</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CEL_HUMAN CEL_HUMAN]] Catalyzes fat and vitamin absorption. Acts in concert with pancreatic lipase and colipase for the complete digestion of dietary triglycerides.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The efficiency of human butyrylcholinesterase (BChE) as a stoichiometric bioscavenger of nerve agents is well established. However, wide use is currently limited by production and purification costs. Aiming at identifying an alternative human protein bioscavenger, we looked for an original scaffold candidate by virtual screening of the Protein Data Bank for functional similarity using the "Surfing the Molecules" software (sumo-pbil.ibcp.fr) and a search model based on the BChE active site topology. Besides the expected acetylcholinesterase and butyrylcholinesterase, we identified a set of bile salt activated lipases structures, among which the human pancreatic lipase (hBAL) that shares 34% identity with BChE. We produced the recombinant enzyme in mammalian cells, purified it, and measured the inhibition constants for paraoxon and surrogates of VX, sarin and tabun. We solved the X-ray structure of apo hBAL and conjugates with paraoxon and the surrogates at resolutions in the 2-A range. These structures allow the assessment of hBAL for scavenging nerve agents. They revealed that hBAL has inverted stereoselectivity for the surrogates of nerve agent compared to human cholinesterases. We observed a remarkable flip of the catalytic histidine driven by the chelation of Zn(2+). Dealkylation of the conjugate, aka aging, was solely observed for paraoxon.

-	~~Authors:~~ Touvrey, C., ~~Brazzolotto~~, X., Nachon, F.	+	X-ray structures of human bile-salt activated lipase conjugated to nerve agents surrogates.,Touvrey C, Courageux C, Guillon V, Terreux R, Nachon F, Brazzolotto X Toxicology. 2019 Jan 1;411:15-23. doi: 10.1016/j.tox.2018.10.015. Epub 2018 Oct, 22. PMID:30359675<ref>PMID:30359675</ref>

-	~~Description: Crystal structure~~ of ~~VX surrogate NEMP inhibited recombinant human bile salt activated lipase~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Nachon, F~~]]	+	<div class="pdbe-citations 6h1a" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Brazzolotto, X]]		[[Category: Brazzolotto, X]]
		+	[[Category: Nachon, F]]
	[[Category: Touvrey, C]]		[[Category: Touvrey, C]]
		+	[[Category: Alpha-beta hydrolase]]
		+	[[Category: Hydrolase]]
		+	[[Category: Lipase]]
		+	[[Category: Tabun inhibition]]

OCA: Protected "6h1a" [edit=sysop:move=sysop]

OCA — Wed, 18 Jul 2018 05:53:37 GMT

Protected "6h1a" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:53, 18 July 2018

OCA: New page: '''Unreleased structure''' The entry 6h1a is ON HOLD until Paper Publication Authors: Touvrey, C., Brazzolotto, X., Nachon, F. Description: Crystal structure of VX surrogate NEMP inhib...

OCA — Wed, 18 Jul 2018 05:53:34 GMT

New page: '''Unreleased structure''' The entry 6h1a is ON HOLD until Paper Publication Authors: Touvrey, C., Brazzolotto, X., Nachon, F. Description: Crystal structure of VX surrogate NEMP inhib...

New page

'''Unreleased structure'''

The entry 6h1a is ON HOLD until Paper Publication

Authors: Touvrey, C., Brazzolotto, X., Nachon, F.

Description: Crystal structure of VX surrogate NEMP inhibited recombinant human bile salt activated lipase
[[Category: Unreleased Structures]]
[[Category: Nachon, F]]
[[Category: Brazzolotto, X]]
[[Category: Touvrey, C]]

6h1a - Revision history

OCA at 06:36, 27 March 2019

OCA: Protected "6h1a" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6h1a is ON HOLD until Paper Publication Authors: Touvrey, C., Brazzolotto, X., Nachon, F. Description: Crystal structure of VX surrogate NEMP inhib...