5bpa - Revision history

OCA at 12:17, 6 March 2024

OCA — Wed, 06 Mar 2024 12:17:33 GMT

←Older revision		Revision as of 12:17, 6 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5bpa]] 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=5BPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BPA FirstGlance]. <br>		<table><tr><td colspan='2'>[[5bpa]] 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=5BPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BPA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4UF:4-{[({5-[2-(ETHOXYCARBONYL)-1H-INDOL-5-YL]-1-METHYL-1H-PYRAZOL-3-YL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>4UF</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]] 1.79Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4UF:4-{[({5-[2-(ETHOXYCARBONYL)-1H-INDOL-5-YL]-1-METHYL-1H-PYRAZOL-3-YL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>4UF</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=5bpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpa OCA], [https://pdbe.org/5bpa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bpa RCSB], [https://www.ebi.ac.uk/pdbsum/5bpa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpa 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=5bpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpa OCA], [https://pdbe.org/5bpa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bpa RCSB], [https://www.ebi.ac.uk/pdbsum/5bpa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpa ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== 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 5bpa" style="background-color:#fffaf0;"></div>

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

OCA at 06:02, 7 June 2023

OCA — Wed, 07 Jun 2023 06:02:37 GMT

←Older revision		Revision as of 06:02, 7 June 2023
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	<StructureSection load='5bpa' size='340' side='right'caption='[[5bpa]], [[Resolution\|resolution]] 1.79Å' scene=''>		<StructureSection load='5bpa' size='340' side='right'caption='[[5bpa]], [[Resolution\|resolution]] 1.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5bpa]] 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=5BPA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5BPA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5bpa]] 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=5BPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BPA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4UF:4-{[({5-[2-(ETHOXYCARBONYL)-1H-INDOL-5-YL]-1-METHYL-1H-PYRAZOL-3-YL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>4UF</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=4UF:4-{[({5-[2-(ETHOXYCARBONYL)-1H-INDOL-5-YL]-1-METHYL-1H-PYRAZOL-3-YL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>4UF</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]]</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=5bpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpa OCA], [https://pdbe.org/5bpa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bpa RCSB], [https://www.ebi.ac.uk/pdbsum/5bpa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpa 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=5bpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpa OCA], [~~http~~://pdbe.org/5bpa PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5bpa RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5bpa PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpa 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 ==
Line 29:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Farrow~~, N A~~]]	+	[[Category: Farrow NA]]
-	[[Category: Margarit~~, S M]]~~	+	[[Category: Margarit SM]]
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Ridgefield~~]]	+

OCA at 08:53, 11 March 2020

OCA — Wed, 11 Mar 2020 08:53:00 GMT

←Older revision		Revision as of 08:53, 11 March 2020
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	==X-RAY Co-structure of MMP-13 with 4-[({5-[2-(ethoxycarbonyl)-1H-indol-5-yl]-1-methyl-1H-pyrazol-3-yl}formamido)methyl]benzoate==		==X-RAY Co-structure of MMP-13 with 4-[({5-[2-(ethoxycarbonyl)-1H-indol-5-yl]-1-methyl-1H-pyrazol-3-yl}formamido)methyl]benzoate==
-	<StructureSection load='5bpa' size='340' side='right' caption='[[5bpa]], [[Resolution\|resolution]] 1.79Å' scene=''>	+	<StructureSection load='5bpa' size='340' side='right'caption='[[5bpa]], [[Resolution\|resolution]] 1.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5bpa]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BPA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5bpa]] 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=5BPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BPA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4UF:4-{[({5-[2-(ETHOXYCARBONYL)-1H-INDOL-5-YL]-1-METHYL-1H-PYRAZOL-3-YL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>4UF</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=4UF:4-{[({5-[2-(ETHOXYCARBONYL)-1H-INDOL-5-YL]-1-METHYL-1H-PYRAZOL-3-YL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>4UF</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]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5boy\|5boy]]</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=5bpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpa OCA], [http://pdbe.org/5bpa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bpa RCSB], [http://www.ebi.ac.uk/pdbsum/5bpa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpa 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=5bpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpa OCA], [http://pdbe.org/5bpa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bpa RCSB], [http://www.ebi.ac.uk/pdbsum/5bpa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpa ProSAT]</span></td></tr>
	</table>		</table>
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5bpa" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5bpa" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Matrix metalloproteinase 3D structures\|Matrix metalloproteinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Farrow, N A]]		[[Category: Farrow, N A]]
	[[Category: Margarit, S M]]		[[Category: Margarit, S M]]

OCA at 06:55, 26 July 2016

OCA — Tue, 26 Jul 2016 06:55:39 GMT

←Older revision		Revision as of 06:55, 26 July 2016
Line 1:		Line 1:
		+
	==X-RAY Co-structure of MMP-13 with 4-[({5-[2-(ethoxycarbonyl)-1H-indol-5-yl]-1-methyl-1H-pyrazol-3-yl}formamido)methyl]benzoate==		==X-RAY Co-structure of MMP-13 with 4-[({5-[2-(ethoxycarbonyl)-1H-indol-5-yl]-1-methyl-1H-pyrazol-3-yl}formamido)methyl]benzoate==
	<StructureSection load='5bpa' size='340' side='right' caption='[[5bpa]], [[Resolution\|resolution]] 1.79Å' scene=''>		<StructureSection load='5bpa' size='340' side='right' caption='[[5bpa]], [[Resolution\|resolution]] 1.79Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4UF:4-{[({5-[2-(ETHOXYCARBONYL)-1H-INDOL-5-YL]-1-METHYL-1H-PYRAZOL-3-YL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>4UF</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=4UF:4-{[({5-[2-(ETHOXYCARBONYL)-1H-INDOL-5-YL]-1-METHYL-1H-PYRAZOL-3-YL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>4UF</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]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5boy\|5boy]]</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=5bpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpa OCA], [http://pdbe.org/5bpa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bpa RCSB], [http://www.ebi.ac.uk/pdbsum/5bpa 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=5bpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpa OCA], [http://pdbe.org/5bpa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bpa RCSB], [http://www.ebi.ac.uk/pdbsum/5bpa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpa ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 07:47, 7 October 2015

OCA — Wed, 07 Oct 2015 07:47:23 GMT

←Older revision		Revision as of 07:47, 7 October 2015
Line 5:		Line 5:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4UF:4-{[({5-[2-(ETHOXYCARBONYL)-1H-INDOL-5-YL]-1-METHYL-1H-PYRAZOL-3-YL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>4UF</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=4UF:4-{[({5-[2-(ETHOXYCARBONYL)-1H-INDOL-5-YL]-1-METHYL-1H-PYRAZOL-3-YL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>4UF</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]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5boy\|5boy]]</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=5bpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5bpa RCSB], [http://www.ebi.ac.uk/pdbsum/5bpa 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=5bpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpa OCA], [http://pdbe.org/5bpa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bpa RCSB], [http://www.ebi.ac.uk/pdbsum/5bpa PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 19:
	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 5bpa" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:17, 17 June 2015

OCA — Wed, 17 Jun 2015 15:17:45 GMT

←Older revision		Revision as of 15:17, 17 June 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==X-RAY Co-structure of MMP-13 with 4-[({5-[2-(ethoxycarbonyl)-1H-indol-5-yl]-1-methyl-1H-pyrazol-3-yl}formamido)methyl]benzoate==
		+	<StructureSection load='5bpa' size='340' side='right' caption='[[5bpa]], [[Resolution\|resolution]] 1.79Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5bpa]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BPA FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4UF:4-{[({5-[2-(ETHOXYCARBONYL)-1H-INDOL-5-YL]-1-METHYL-1H-PYRAZOL-3-YL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>4UF</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]]</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=5bpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5bpa RCSB], [http://www.ebi.ac.uk/pdbsum/5bpa 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 5bpa 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., Margarit,~~ S.M.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~X-RAY Co-structure of MMP-13 with 4-~~[~~({5-~~[~~2-(ethoxycarbonyl)-1H-indol-5-yl~~]~~-1-methyl-1H-pyrazol-3-yl}formamido)methyl~~]~~benzoate~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: ~~Farrow, N.A~~]]	+	__TOC__
-	[[Category: ~~Margarit, S.M~~]]	+	</StructureSection>
		+	[[Category: Farrow, N A]]
		+	[[Category: Margarit, S M]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Protease]]
		+	[[Category: Ridgefield]]

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

OCA — Wed, 03 Jun 2015 11:45:30 GMT

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

←Older revision

Revision as of 11:45, 3 June 2015

OCA: New page: '''Unreleased structure''' The entry 5bpa is ON HOLD Authors: Farrow, N.A., Margarit, S.M. Description: X-RAY Co-structure of MMP-13 with 4-[({5-[2-(ethoxycarbonyl)-1H-indol-5-yl]-1-me...

OCA — Wed, 03 Jun 2015 11:45:29 GMT

New page: '''Unreleased structure''' The entry 5bpa is ON HOLD Authors: Farrow, N.A., Margarit, S.M. Description: X-RAY Co-structure of MMP-13 with 4-[({5-[2-(ethoxycarbonyl)-1H-indol-5-yl]-1-me...

New page

'''Unreleased structure'''

The entry 5bpa is ON HOLD

Authors: Farrow, N.A., Margarit, S.M.

Description: X-RAY Co-structure of MMP-13 with 4-[({5-[2-(ethoxycarbonyl)-1H-indol-5-yl]-1-methyl-1H-pyrazol-3-yl}formamido)methyl]benzoate
[[Category: Unreleased Structures]]
[[Category: Farrow, N.A]]
[[Category: Margarit, S.M]]