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5bot

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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==
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<StructureSection load='5bot' size='340' side='right' caption='[[5bot]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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<StructureSection load='5bot' size='340' side='right'caption='[[5bot]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<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>
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<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>
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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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5boy|5boy]], [[5bpa|5bpa]]</td></tr>
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<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>
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<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>
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<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>
== Disease ==
== Disease ==
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[[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>
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[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 ==
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[[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.
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[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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 &gt;100-fold selective over nine other MMP isoforms tested.
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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>
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==See Also==
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*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
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</div>
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<div class="pdbe-citations 5bot" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Farrow, N A]]
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[[Category: Homo sapiens]]
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[[Category: Padyana, A K]]
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[[Category: Large Structures]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Farrow NA]]
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[[Category: Protease]]
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[[Category: Padyana AK]]
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[[Category: Ridgefield]]
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Current revision

X-RAY Co-structure of MMP-13 with ethyl 5-carbamoyl-1H-indole-2-carboxylate

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