6f6r - Revision history

OCA at 07:49, 23 May 2018

OCA — Wed, 23 May 2018 07:49:41 GMT

←Older revision		Revision as of 07:49, 23 May 2018
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	<StructureSection load='6f6r' size='340' side='right' caption='[[6f6r]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='6f6r' size='340' side='right' caption='[[6f6r]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6f6r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F6R FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6f6r]] 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=6F6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F6R FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CVE:(3~{S})-3-[[(2~{R})-2-[3-methyl-2,6-bis(oxidanylidene)-5-[[4-(quinoxalin-2-ylamino)phenyl]carbonylamino]pyrimidin-1-yl]propanoyl]amino]-4-oxidanyl-butanoic+acid'>CVE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CVE:(3~{S})-3-[[(2~{R})-2-[3-methyl-2,6-bis(oxidanylidene)-5-[[4-(quinoxalin-2-ylamino)phenyl]carbonylamino]pyrimidin-1-yl]propanoyl]amino]-4-oxidanyl-butanoic+acid'>CVE</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">CASP1, IL1BC, IL1BCE ([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/Caspase-1 Caspase-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.36 3.4.22.36] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-1 Caspase-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.36 3.4.22.36] </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=6f6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f6r OCA], [http://pdbe.org/6f6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f6r RCSB], [http://www.ebi.ac.uk/pdbsum/6f6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f6r 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=6f6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f6r OCA], [http://pdbe.org/6f6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f6r RCSB], [http://www.ebi.ac.uk/pdbsum/6f6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f6r ProSAT]</span></td></tr>
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	</StructureSection>		</StructureSection>
	[[Category: Caspase-1]]		[[Category: Caspase-1]]
		+	[[Category: Human]]
	[[Category: Aubert, J]]		[[Category: Aubert, J]]
	[[Category: Aurelly, M]]		[[Category: Aurelly, M]]

OCA at 08:15, 2 May 2018

OCA — Wed, 02 May 2018 08:15:59 GMT

←Older revision		Revision as of 08:15, 2 May 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6f6r is ~~ON HOLD~~ ~~until sometime~~ in the ~~future~~	+	==Crystal structure of human Caspase-1 with N-{3-[1-((S)-2-Hydroxy-5-oxo-tetrahydro-furan-3-ylcarbamoyl)-ethyl]-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl}-4-(quinoxalin-2-ylamino)-benzamide==
		+	<StructureSection load='6f6r' size='340' side='right' caption='[[6f6r]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6f6r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F6R FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CVE:(3~{S})-3-[[(2~{R})-2-[3-methyl-2,6-bis(oxidanylidene)-5-[[4-(quinoxalin-2-ylamino)phenyl]carbonylamino]pyrimidin-1-yl]propanoyl]amino]-4-oxidanyl-butanoic+acid'>CVE</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'>[http://en.wikipedia.org/wiki/Caspase-1 Caspase-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.36 3.4.22.36] </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=6f6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f6r OCA], [http://pdbe.org/6f6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f6r RCSB], [http://www.ebi.ac.uk/pdbsum/6f6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f6r ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CASP1_HUMAN CASP1_HUMAN]] Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis.<ref>PMID:7876192</ref> <ref>PMID:15498465</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The use of an interleukin beta antibody is currently being investigated in the clinic for the treatment of acne, a dermatological disorder affecting 650M persons globally. Inhibiting the protease responsible for the cleavage of inactive pro-IL1beta into active IL-1beta, caspase-1, could be an alternative small molecule approach. This report describes the discovery of uracil 20, a potent (38 nM in THP1 cells assay) caspase-1 inhibitor for the topical treatment of inflammatory acne. The uracil series was designed according to a published caspase-1 pharmacophore model involving a reactive warhead in P1 for covalent reversible inhibition and an aryl moiety in P4 for selectivity against the apoptotic caspases. Reversibility was assessed in an enzymatic dilution assay or by using different substrate concentrations. In addition to classical structure-activity-relationship exploration, topical administration challenges such as phototoxicity, organic and aqueous solubility, chemical stability in solution, and skin metabolic stability are discussed and successfully resolved.

-	~~Authors: Isabet, T~~., ~~Chantalat~~, L., ~~Thoreau~~, E.	+	Rational Drug Design of Topically Administered Caspase 1 Inhibitors for the Treatment of Inflammatory Acne.,Fournier JF, Clary L, Chambon S, Dumais L, Harris CS, Millois C, Pierre R, Talano S, Thoreau E, Aubert J, Aurelly M, Bouix-Peter C, Brethon A, Chantalat L, Christin O, Comino C, El-Bazbouz G, Ghilini AL, Isabet T, Lardy C, Luzy AP, Mathieu C, Mebrouk K, Orfila D, Pascau J, Reverse K, Roche D, Rodeschini V, Hennequin LF J Med Chem. 2018 Apr 24. doi: 10.1021/acs.jmedchem.8b00067. PMID:29648825<ref>PMID:29648825</ref>

-	~~Description: Crystal structure~~ of ~~human Caspase~~-~~1 with N-{3~~-[1-((S~~)-2-Hydroxy-5-oxo-tetrahydro-furan-3-ylcarbamoyl)-ethyl~~]~~-1-methyl-2~~,~~4-dioxo-1~~,2,3,~~4-tetrahydro-pyrimidin~~-~~5-yl}-4-(quinoxalin-2-ylamino)-benzamide~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6f6r" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Caspase-1]]
		+	[[Category: Aubert, J]]
		+	[[Category: Aurelly, M]]
		+	[[Category: Bouix-Peter, C]]
		+	[[Category: Brethon, A]]
		+	[[Category: Chambon, S]]
		+	[[Category: Chantalat, L]]
		+	[[Category: Christin, O]]
		+	[[Category: Clary, L]]
		+	[[Category: Comino, C]]
		+	[[Category: Dumais, L]]
		+	[[Category: El-Bazbouz, G]]
		+	[[Category: Fournier, J F]]
		+	[[Category: Ghilini, A L]]
		+	[[Category: Harris, C S]]
		+	[[Category: Hennequin, L F]]
	[[Category: Isabet, T]]		[[Category: Isabet, T]]
		+	[[Category: Lardy, C]]
		+	[[Category: Luzy, A P]]
		+	[[Category: Mathieu, C]]
		+	[[Category: Mebrouk, K]]
		+	[[Category: Millois-Barbuis, C]]
		+	[[Category: Orfila, D]]
		+	[[Category: Pascau, J]]
		+	[[Category: Pierre, R]]
		+	[[Category: Reverse, K]]
		+	[[Category: Roche, D]]
		+	[[Category: Rodeschini, V]]
		+	[[Category: Talano, S]]
	[[Category: Thoreau, E]]		[[Category: Thoreau, E]]
-	[[Category: ~~Chantalat, L~~]]	+	[[Category: Hydrolase]]
		+	[[Category: Inflammatory disease]]
		+	[[Category: Nanomolar inhibitor]]
		+	[[Category: Sp3 hybridization]]

OCA: Protected "6f6r" [edit=sysop:move=sysop]

OCA — Wed, 13 Dec 2017 06:03:00 GMT

Protected "6f6r" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:03, 13 December 2017

OCA: New page: '''Unreleased structure''' The entry 6f6r is ON HOLD until sometime in the future Authors: Isabet, T., Chantalat, L., Thoreau, E. Description: Crystal structure of human Caspase-1 with...

OCA — Wed, 13 Dec 2017 06:02:59 GMT

New page: '''Unreleased structure''' The entry 6f6r is ON HOLD until sometime in the future Authors: Isabet, T., Chantalat, L., Thoreau, E. Description: Crystal structure of human Caspase-1 with...

New page

'''Unreleased structure'''

The entry 6f6r is ON HOLD until sometime in the future

Authors: Isabet, T., Chantalat, L., Thoreau, E.

Description: Crystal structure of human Caspase-1 with N-{3-[1-((S)-2-Hydroxy-5-oxo-tetrahydro-furan-3-ylcarbamoyl)-ethyl]-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl}-4-(quinoxalin-2-ylamino)-benzamide
[[Category: Unreleased Structures]]
[[Category: Isabet, T]]
[[Category: Thoreau, E]]
[[Category: Chantalat, L]]