6ela - Revision history

OCA at 06:21, 6 June 2018

OCA — Wed, 06 Jun 2018 06:21:28 GMT

←Older revision		Revision as of 06:21, 6 June 2018
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	<StructureSection load='6ela' size='340' side='right' caption='[[6ela]], [[Resolution\|resolution]] 1.48Å' scene=''>		<StructureSection load='6ela' size='340' side='right' caption='[[6ela]], [[Resolution\|resolution]] 1.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ela]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ELA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ELA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ela]] is a 4 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=6ELA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ELA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B9Z:(2~{S})-2-[2-[4-(4-methoxyphenyl)phenyl]sulfanylphenyl]pentanedioic+acid'>B9Z</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B9Z:(2~{S})-2-[2-[4-(4-methoxyphenyl)phenyl]sulfanylphenyl]pentanedioic+acid'>B9Z</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ekn\|6ekn]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ekn\|6ekn]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MMP12, HME ([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/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] </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=6ela FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ela OCA], [http://pdbe.org/6ela PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ela RCSB], [http://www.ebi.ac.uk/pdbsum/6ela PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ela 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=6ela FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ela OCA], [http://pdbe.org/6ela PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ela RCSB], [http://www.ebi.ac.uk/pdbsum/6ela PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ela ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Macrophage elastase]]		[[Category: Macrophage elastase]]
	[[Category: Ciccone, L]]		[[Category: Ciccone, L]]

OCA at 05:34, 16 May 2018

OCA — Wed, 16 May 2018 05:34:28 GMT

←Older revision		Revision as of 05:34, 16 May 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6ela is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of MMP12 in complex with inhibitor BE4.==
		+	<StructureSection load='6ela' size='340' side='right' caption='[[6ela]], [[Resolution\|resolution]] 1.48Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ela]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ELA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ELA FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B9Z:(2~{S})-2-[2-[4-(4-methoxyphenyl)phenyl]sulfanylphenyl]pentanedioic+acid'>B9Z</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ekn\|6ekn]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] </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=6ela FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ela OCA], [http://pdbe.org/6ela PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ela RCSB], [http://www.ebi.ac.uk/pdbsum/6ela PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ela ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MMP12_HUMAN MMP12_HUMAN]] May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Matrix metalloproteinase-12 (MMP-12) selective inhibitors could play a role in the treatment of lung inflammatory and cardiovascular diseases. In the present study, the previously reported 4-methoxybiphenylsulfonyl hydroxamate and carboxylate-based inhibitors (1b and 2b) were modified to enhance their selectivity for MMP-12. In the newly synthesized thioaryl derivatives, the nature of the zinc binding group (ZBG) and the sulfur oxidation state were changed. Biological assays carried out in vitro on human MMPs with the resulting compounds led to identify a sulfide, 4a, bearing a N-1-hydroxypiperidine-2,6-dione (HPD) group as new ZBG. 4a is a promising hit compound since it displayed a nanomolar affinity for MMP-12 with a marked selectivity over MMP-9, MMP-1 and MMP-14. Solution complexation studies with Zn2+ were performed to characterize the chelating abilities of the new compounds and confirmed the bidentate binding mode of HPD derivatives. X-ray crystallography studies using MMP-12 and MMP-9 catalytic domains were carried out to rationalize the biological results.

-	~~Authors~~: ~~Ciccone~~, L., ~~Tepshi, L~~., Nuti, E., ~~Rossello~~, A., ~~Stura~~, E.A.	+	Development of Thioaryl-based Matrix Metalloproteinase-12 Inhibitors with Alternative Zinc-Binding Groups: Synthesis, Potentiometric, NMR and Crystallographic Studies.,Nuti E, Cuffaro D, Bernardini E, Camodeca C, Panelli L, Chaves S, Ciccone L, Tepshi L, Vera L, Orlandini E, Nencetti S, Stura EA, Santos MA, Dive V, Rossello A J Med Chem. 2018 May 4. doi: 10.1021/acs.jmedchem.8b00096. PMID:29727184<ref>PMID:29727184</ref>

-	~~Description: Crystal structure~~ of ~~MMP12 in complex with inhibitor BE4~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6ela" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Macrophage elastase]]
	[[Category: Ciccone, L]]		[[Category: Ciccone, L]]
-	[[Category: Rossello, A]]
	[[Category: Nuti, E]]		[[Category: Nuti, E]]
		+	[[Category: Rossello, A]]
		+	[[Category: Stura, E A]]
	[[Category: Tepshi, L]]		[[Category: Tepshi, L]]
-	[[Category: ~~Stura, E.A~~]]	+	[[Category: Carboxylate inhibitor alternative zinc-binding group]]
		+	[[Category: Hydrolase]]
		+	[[Category: Metzincin]]

OCA at 06:39, 8 November 2017

OCA — Wed, 08 Nov 2017 06:39:58 GMT

←Older revision		Revision as of 06:39, 8 November 2017
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Ciccone, L., Tepshi, L., Nuti, E., Rossello, A., Stura, E.A.		Authors: Ciccone, L., Tepshi, L., Nuti, E., Rossello, A., Stura, E.A.

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

OCA — Wed, 04 Oct 2017 08:20:35 GMT

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

←Older revision

Revision as of 08:20, 4 October 2017

OCA: New page: '''Unreleased structure''' The entry 6ela is ON HOLD Authors: Ciccone, L., Tepshi, L., Nuti, E., Rossello, A., Stura, E.A. Description: Crystal structure of MMP12 in complex with inhib...

OCA — Wed, 04 Oct 2017 08:20:34 GMT

New page: '''Unreleased structure''' The entry 6ela is ON HOLD Authors: Ciccone, L., Tepshi, L., Nuti, E., Rossello, A., Stura, E.A. Description: Crystal structure of MMP12 in complex with inhib...

New page

'''Unreleased structure'''

The entry 6ela is ON HOLD

Authors: Ciccone, L., Tepshi, L., Nuti, E., Rossello, A., Stura, E.A.

Description: Crystal structure of MMP12 in complex with inhibitor BE4.
[[Category: Unreleased Structures]]
[[Category: Ciccone, L]]
[[Category: Rossello, A]]
[[Category: Nuti, E]]
[[Category: Tepshi, L]]
[[Category: Stura, E.A]]