5bot - Revision history

OCA at 12:17, 6 March 2024

2024-03-06T12:17:30Z

← Older revision		Revision as of 12:17, 6 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5bot]] 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=5BOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BOT FirstGlance]. <br>		<table><tr><td colspan='2'>[[5bot]] 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=5BOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BOT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4UM:ETHYL+5-CARBAMOYL-1H-INDOLE-2-CARBOXYLATE'>4UM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.85Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4UM:ETHYL+5-CARBAMOYL-1H-INDOLE-2-CARBOXYLATE'>4UM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5bot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bot OCA], [https://pdbe.org/5bot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bot RCSB], [https://www.ebi.ac.uk/pdbsum/5bot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bot 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=5bot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bot OCA], [https://pdbe.org/5bot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bot RCSB], [https://www.ebi.ac.uk/pdbsum/5bot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bot ProSAT]</span></td></tr>
	</table>		</table>
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN] Degrades collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process.		[https://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN] Degrades collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process.
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Matrix metalloproteases (MMPs) play an important role in cartilage homeostasis under both normal and inflamed disease states and, thus, have become attractive targets for the treatment of arthritic diseases. Herein, we describe the identification of a potent, selective MMP-13 inhibitor, developed using fragment-based structure-guided lead identification and optimization techniques. Virtual screening methods identified a novel, indole-based MMP-13 inhibitor that bound into the S1' pocket of the protein exhibiting a novel interaction pattern hitherto not observed in MMP-13 inhibitors. X-ray crystallographic structures were used to guide the elaboration of the fragment, ultimately leading to a potent inhibitor that was >100-fold selective over nine other MMP isoforms tested.

	Fragment-based discovery of indole inhibitors of matrix metalloproteinase-13.,Taylor SJ, Abeywardane A, Liang S, Muegge I, Padyana AK, Xiong Z, Hill-Drzewi M, Farmer B, Li X, Collins B, Li JX, Heim-Riether A, Proudfoot J, Zhang Q, Goldberg D, Zuvela-Jelaska L, Zaher H, Li J, Farrow NA J Med Chem. 2011 Dec 8;54(23):8174-87. doi: 10.1021/jm201129m. Epub 2011 Nov 9. PMID:22017539<ref>PMID:22017539</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 5bot" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==

OCA at 06:02, 7 June 2023

2023-06-07T06:02:19Z

← Older revision		Revision as of 06:02, 7 June 2023
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	==X-RAY Co-structure of MMP-13 with ethyl 5-carbamoyl-1H-indole-2-carboxylate==		==X-RAY Co-structure of MMP-13 with ethyl 5-carbamoyl-1H-indole-2-carboxylate==
	<StructureSection load='5bot' size='340' side='right' caption='[[5bot]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='5bot' size='340' side='right'caption='[[5bot]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5bot]] 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=5BOT OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5BOT FirstGlance]. <br>		<table><tr><td colspan='2'>[[5bot]] 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=5BOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BOT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4UM:ETHYL+5-CARBAMOYL-1H-INDOLE-2-CARBOXYLATE'>4UM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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" id="ligandDat"><scene name='pdbligand=4UM:ETHYL+5-CARBAMOYL-1H-INDOLE-2-CARBOXYLATE'>4UM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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">[[5boy\|5boy]], [[5bpa\|5bpa]]</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=5bot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bot OCA], [https://pdbe.org/5bot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bot RCSB], [https://www.ebi.ac.uk/pdbsum/5bot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bot ProSAT]</span></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MMP13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=5bot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bot OCA], [~~http~~://pdbe.org/5bot PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5bot RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5bot PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5bot ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[~~[http~~://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN]] Defects in MMP13 are the cause of spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO) [MIM:[~~http~~://omim.org/entry/602111 602111]]. A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age.<ref>PMID:16167086</ref> Defects in MMP13 are the cause of metaphyseal anadysplasia type 1 (MANDP1) [MIM:[~~http~~://omim.org/entry/602111 602111]]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.<ref>PMID:19615667</ref>		[https://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN] Defects in MMP13 are the cause of spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO) [MIM:[https://omim.org/entry/602111 602111]. A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age.<ref>PMID:16167086</ref> Defects in MMP13 are the cause of metaphyseal anadysplasia type 1 (MANDP1) [MIM:[https://omim.org/entry/602111 602111]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.<ref>PMID:19615667</ref>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN]] Degrades collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process.		[https://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN] Degrades collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
	*[[Matrix metalloproteinase\|Matrix metalloproteinase]]		*[[Matrix metalloproteinase 3D structures\|Matrix metalloproteinase 3D structures]]
	*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]		*[[Ubiquitin protein ligase 3D structures\|Ubiquitin protein ligase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Farrow, N A~~]]		[[Category: Large Structures]]
	[[Category: ~~Padyana, A K~~]]		[[Category: Farrow NA]]
	[[Category: ~~Hydrolase-hydrolase inhibitor complex]]~~		[[Category: Padyana AK]]
	~~[[Category: Protease]]~~
	~~[[Category: Ridgefield~~]]

OCA at 07:59, 14 June 2018

2018-06-14T07:59:16Z

← Older revision		Revision as of 07:59, 14 June 2018
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	<StructureSection load='5bot' size='340' side='right' caption='[[5bot]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='5bot' size='340' side='right' caption='[[5bot]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5bot]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BOT FirstGlance]. <br>		<table><tr><td colspan='2'>[[5bot]] 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=5BOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BOT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4UM:ETHYL+5-CARBAMOYL-1H-INDOLE-2-CARBOXYLATE'>4UM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=4UM:ETHYL+5-CARBAMOYL-1H-INDOLE-2-CARBOXYLATE'>4UM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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">[[5boy\|5boy]], [[5bpa\|5bpa]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5boy\|5boy]], [[5bpa\|5bpa]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MMP13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5bot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bot OCA], [http://pdbe.org/5bot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bot RCSB], [http://www.ebi.ac.uk/pdbsum/5bot PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bot 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=5bot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bot OCA], [http://pdbe.org/5bot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bot RCSB], [http://www.ebi.ac.uk/pdbsum/5bot PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bot ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 5bot" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5bot" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Matrix metalloproteinase\|Matrix metalloproteinase]]
			*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
	[[Category: Farrow, N A]]		[[Category: Farrow, N A]]
	[[Category: Padyana, A K]]		[[Category: Padyana, A K]]

OCA at 08:12, 27 July 2016

2016-07-27T08:12:29Z

← Older revision		Revision as of 08:12, 27 July 2016
Line 1:		Line 1:

	==X-RAY Co-structure of MMP-13 with ethyl 5-carbamoyl-1H-indole-2-carboxylate==		==X-RAY Co-structure of MMP-13 with ethyl 5-carbamoyl-1H-indole-2-carboxylate==
	<StructureSection load='5bot' size='340' side='right' caption='[[5bot]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='5bot' size='340' side='right' caption='[[5bot]], [[Resolution\|resolution]] 1.85Å' scene=''>
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	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4UM:ETHYL+5-CARBAMOYL-1H-INDOLE-2-CARBOXYLATE'>4UM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=4UM:ETHYL+5-CARBAMOYL-1H-INDOLE-2-CARBOXYLATE'>4UM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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">[[5boy\|5boy]], [[5bpa\|5bpa]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5boy\|5boy]], [[5bpa\|5bpa]]</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=5bot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bot OCA], [http://pdbe.org/5bot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bot RCSB], [http://www.ebi.ac.uk/pdbsum/5bot PDBsum]</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=5bot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bot OCA], [http://pdbe.org/5bot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bot RCSB], [http://www.ebi.ac.uk/pdbsum/5bot PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bot ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 07:42, 7 October 2015

2015-10-07T07:42:45Z

← Older revision		Revision as of 07:42, 7 October 2015
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	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4UM:ETHYL+5-CARBAMOYL-1H-INDOLE-2-CARBOXYLATE'>4UM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=4UM:ETHYL+5-CARBAMOYL-1H-INDOLE-2-CARBOXYLATE'>4UM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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">[[5boy\|5boy]], [[5bpa\|5bpa]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5boy\|5boy]], [[5bpa\|5bpa]]</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=5bot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bot OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5bot RCSB], [http://www.ebi.ac.uk/pdbsum/5bot PDBsum]</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=5bot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bot OCA], [http://pdbe.org/5bot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bot RCSB], [http://www.ebi.ac.uk/pdbsum/5bot PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 5bot" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:15, 17 June 2015

2015-06-17T15:15:40Z

← Older revision		Revision as of 15:15, 17 June 2015
Line 1:		Line 1:
	'''~~Unreleased~~ structure'''		==X-RAY Co-structure of MMP-13 with ethyl 5-carbamoyl-1H-indole-2-carboxylate==
			<StructureSection load='5bot' size='340' side='right' caption='[[5bot]], [[Resolution\|resolution]] 1.85Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[5bot]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BOT FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4UM:ETHYL+5-CARBAMOYL-1H-INDOLE-2-CARBOXYLATE'>4UM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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">[[5boy\|5boy]], [[5bpa\|5bpa]]</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=5bot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bot OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5bot RCSB], [http://www.ebi.ac.uk/pdbsum/5bot PDBsum]</span></td></tr>
			</table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN]] Defects in MMP13 are the cause of spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO) [MIM:[http://omim.org/entry/602111 602111]]. A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age.<ref>PMID:16167086</ref> Defects in MMP13 are the cause of metaphyseal anadysplasia type 1 (MANDP1) [MIM:[http://omim.org/entry/602111 602111]]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.<ref>PMID:19615667</ref>
			== Function ==
			[[http://www.uniprot.org/uniprot/MMP13_HUMAN MMP13_HUMAN]] Degrades collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Matrix metalloproteases (MMPs) play an important role in cartilage homeostasis under both normal and inflamed disease states and, thus, have become attractive targets for the treatment of arthritic diseases. Herein, we describe the identification of a potent, selective MMP-13 inhibitor, developed using fragment-based structure-guided lead identification and optimization techniques. Virtual screening methods identified a novel, indole-based MMP-13 inhibitor that bound into the S1' pocket of the protein exhibiting a novel interaction pattern hitherto not observed in MMP-13 inhibitors. X-ray crystallographic structures were used to guide the elaboration of the fragment, ultimately leading to a potent inhibitor that was >100-fold selective over nine other MMP isoforms tested.

	~~The entry 5bot is ON HOLD~~		Fragment-based discovery of indole inhibitors of matrix metalloproteinase-13.,Taylor SJ, Abeywardane A, Liang S, Muegge I, Padyana AK, Xiong Z, Hill-Drzewi M, Farmer B, Li X, Collins B, Li JX, Heim-Riether A, Proudfoot J, Zhang Q, Goldberg D, Zuvela-Jelaska L, Zaher H, Li J, Farrow NA J Med Chem. 2011 Dec 8;54(23):8174-87. doi: 10.1021/jm201129m. Epub 2011 Nov 9. PMID:22017539<ref>PMID:22017539</ref>

	~~Authors~~: Farrow, N.A., Padyana, A.K.		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~Description: X-RAY Co-structure of MMP-13 with ethyl 5-carbamoyl-1H-indole-2-carboxylate~~		== References ==
	[[Category: ~~Unreleased Structures~~]]		<references/>
	[[Category: ~~Farrow, N.A~~]]		__TOC__
	[[Category: ~~Padyana, A.K~~]]		</StructureSection>
			[[Category: Farrow, N A]]
			[[Category: Padyana, A K]]
			[[Category: Hydrolase-hydrolase inhibitor complex]]
			[[Category: Protease]]
			[[Category: Ridgefield]]

OCA: Protected "5bot" [edit=sysop:move=sysop]

2015-06-03T11:44:07Z

Protected "5bot" [edit=sysop:move=sysop]

← Older revision	Revision as of 11:44, 3 June 2015
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5bot is ON HOLD Authors: Farrow, N.A., Padyana, A.K. Description: X-RAY Co-structure of MMP-13 with ethyl 5-carbamoyl-1H-indole-2-carboxylate [[Cat...

2015-06-03T11:44:06Z

New page: '''Unreleased structure''' The entry 5bot is ON HOLD Authors: Farrow, N.A., Padyana, A.K. Description: X-RAY Co-structure of MMP-13 with ethyl 5-carbamoyl-1H-indole-2-carboxylate [[Cat...

New page

'''Unreleased structure'''

The entry 5bot is ON HOLD

Authors: Farrow, N.A., Padyana, A.K.

Description: X-RAY Co-structure of MMP-13 with ethyl 5-carbamoyl-1H-indole-2-carboxylate
[[Category: Unreleased Structures]]
[[Category: Farrow, N.A]]
[[Category: Padyana, A.K]]