4jpa

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4jpa]] 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=4JPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JPA FirstGlance]. <br>
<table><tr><td colspan='2'>[[4jpa]] 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=4JPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JPA FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AZ6:3-[({2-[4-({[(4S)-4-METHYL-2,5-DIOXOIMIDAZOLIDIN-4-YL]METHYL}SULFONYL)PIPERAZIN-1-YL]PYRIMIDIN-5-YL}OXY)METHYL]BENZONITRILE'>AZ6</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AZ6:3-[({2-[4-({[(4S)-4-METHYL-2,5-DIOXOIMIDAZOLIDIN-4-YL]METHYL}SULFONYL)PIPERAZIN-1-YL]PYRIMIDIN-5-YL}OXY)METHYL]BENZONITRILE'>AZ6</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jp4|4jp4]]</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jp4|4jp4]]</td></tr>
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<tr><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>
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<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>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jpa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jpa RCSB], [http://www.ebi.ac.uk/pdbsum/4jpa PDBsum]</span></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=4jpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jpa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jpa RCSB], [http://www.ebi.ac.uk/pdbsum/4jpa PDBsum]</span></td></tr>
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<table>
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</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>
[[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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Hydantoin based inhibitors of MMP13--discovery of AZD6605.,De Savi C, Waterson D, Pape A, Lamont S, Hadley E, Mills M, Page KM, Bowyer J, Maciewicz RA Bioorg Med Chem Lett. 2013 Aug 15;23(16):4705-12. doi:, 10.1016/j.bmcl.2013.05.089. Epub 2013 Jun 10. PMID:23810497<ref>PMID:23810497</ref>
Hydantoin based inhibitors of MMP13--discovery of AZD6605.,De Savi C, Waterson D, Pape A, Lamont S, Hadley E, Mills M, Page KM, Bowyer J, Maciewicz RA Bioorg Med Chem Lett. 2013 Aug 15;23(16):4705-12. doi:, 10.1016/j.bmcl.2013.05.089. Epub 2013 Jun 10. PMID:23810497<ref>PMID:23810497</ref>
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
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==See Also==
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*[[Matrix metalloproteinase|Matrix metalloproteinase]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Human]]
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[[Category: Gerhardt, S.]]
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[[Category: Gerhardt, S]]
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[[Category: Hargreaves, D.]]
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[[Category: Hargreaves, D]]
[[Category: Calcium binding]]
[[Category: Calcium binding]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Matrix metalloprotease]]
[[Category: Matrix metalloprotease]]
[[Category: Zinc binding]]
[[Category: Zinc binding]]

Revision as of 14:27, 4 January 2015

Mmp13 in complex with a piperazine hydantoin ligand

4jpa, resolution 2.00Å

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