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| | <StructureSection load='2pjt' size='340' side='right'caption='[[2pjt]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='2pjt' size='340' side='right'caption='[[2pjt]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2pjt]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PJT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2pjt]] is a 4 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=2PJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PJT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=347:TERT-BUTYL+4-({[4-(BUT-2-YN-1-YLAMINO)PHENYL]SULFONYL}METHYL)-4-[(HYDROXYAMINO)CARBONYL]PIPERIDINE-1-CARBOXYLATE'>347</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]] 2.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ztq|1ztq]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=347:TERT-BUTYL+4-({[4-(BUT-2-YN-1-YLAMINO)PHENYL]SULFONYL}METHYL)-4-[(HYDROXYAMINO)CARBONYL]PIPERIDINE-1-CARBOXYLATE'>347</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP13 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2pjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pjt OCA], [https://pdbe.org/2pjt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pjt RCSB], [https://www.ebi.ac.uk/pdbsum/2pjt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pjt 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=2pjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pjt OCA], [https://pdbe.org/2pjt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pjt RCSB], [https://www.ebi.ac.uk/pdbsum/2pjt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pjt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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>
| + | [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 == |
| - | [[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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Huang, A]] | + | [[Category: Huang A]] |
| - | [[Category: Levin, J I]] | + | [[Category: Levin JI]] |
| - | [[Category: Lovering, F]] | + | [[Category: Lovering F]] |
| - | [[Category: Mosyak, L]] | + | [[Category: Mosyak L]] |
| - | [[Category: Xu, Z]] | + | [[Category: Xu Z]] |
| - | [[Category: Calcium]]
| + | |
| - | [[Category: Collagen degradation]]
| + | |
| - | [[Category: Collagenase]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Extracellular matrix]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrophobic s1ss']]
| + | |
| - | [[Category: Hydroxamate]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Metalloprotease]]
| + | |
| - | [[Category: Mmp]]
| + | |
| - | [[Category: Mmp-13]]
| + | |
| - | [[Category: P1' group]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Zinc chelator]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| Structural highlights
Disease
MMP13_HUMAN Defects in MMP13 are the cause of spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO) [MIM: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.[1] Defects in MMP13 are the cause of metaphyseal anadysplasia type 1 (MANDP1) [MIM: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.[2]
Function
MMP13_HUMAN Degrades collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
A series of beta-sulfonyl hydroxamate TACE inhibitors, bearing a butynylamino or a butynyloxy P1' group, was designed and synthesized. Of the compounds investigated, 22 has excellent potency against isolated TACE enzyme, shows good selectivity over MMP-2 and MMP-13, and oral activity in an in vivo mouse model of TNF-alpha production.
Structure-based design of TACE selective inhibitors: manipulations in the S1'-S3' pocket.,Huang A, Joseph-McCarthy D, Lovering F, Sun L, Wang W, Xu W, Zhu Y, Cui J, Zhang Y, Levin JI Bioorg Med Chem. 2007 Sep 15;15(18):6170-81. Epub 2007 Jun 20. PMID:17606376[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kennedy AM, Inada M, Krane SM, Christie PT, Harding B, Lopez-Otin C, Sanchez LM, Pannett AA, Dearlove A, Hartley C, Byrne MH, Reed AA, Nesbit MA, Whyte MP, Thakker RV. MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type (SEMD(MO). J Clin Invest. 2005 Oct;115(10):2832-42. PMID:16167086 doi:10.1172/JCI22900
- ↑ Lausch E, Keppler R, Hilbert K, Cormier-Daire V, Nikkel S, Nishimura G, Unger S, Spranger J, Superti-Furga A, Zabel B. Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia. Am J Hum Genet. 2009 Aug;85(2):168-78. doi: 10.1016/j.ajhg.2009.06.014. Epub 2009, Jul 16. PMID:19615667 doi:10.1016/j.ajhg.2009.06.014
- ↑ Huang A, Joseph-McCarthy D, Lovering F, Sun L, Wang W, Xu W, Zhu Y, Cui J, Zhang Y, Levin JI. Structure-based design of TACE selective inhibitors: manipulations in the S1'-S3' pocket. Bioorg Med Chem. 2007 Sep 15;15(18):6170-81. Epub 2007 Jun 20. PMID:17606376 doi:10.1016/j.bmc.2007.06.031
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