1xuc

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[[Image:1xuc.jpg|left|200px]]
 
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{{Structure
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==Matrix metalloproteinase-13 complexed with non-zinc binding inhibitor==
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|PDB= 1xuc |SIZE=350|CAPTION= <scene name='initialview01'>1xuc</scene>, resolution 1.700&Aring;
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<StructureSection load='1xuc' size='340' side='right'caption='[[1xuc]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=PB3:N,N&#39;-BIS(3-METHYLBENZYL)PYRIMIDINE-4,6-DICARBOXAMIDE'>PB3</scene>
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<table><tr><td colspan='2'>[[1xuc]] 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=1XUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XUC FirstGlance]. <br>
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|ACTIVITY=
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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]] 1.7&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PB3:N,N-BIS(3-METHYLBENZYL)PYRIMIDINE-4,6-DICARBOXAMIDE'>PB3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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}}
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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=1xuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xuc OCA], [https://pdbe.org/1xuc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xuc RCSB], [https://www.ebi.ac.uk/pdbsum/1xuc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xuc ProSAT]</span></td></tr>
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</table>
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== Disease ==
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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>
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== Function ==
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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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xu/1xuc_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1xuc ConSurf].
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<div style="clear:both"></div>
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'''Matrix metalloproteinase-13 complexed with non-zinc binding inhibitor'''
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==See Also==
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*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
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== References ==
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==Overview==
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<references/>
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Inhibitors for matrix metalloproteinases (MMPs) are under investigation for the treatment of cancer, arthritis, and cardiovascular disease. Here, we report a class of highly selective MMP-13 inhibitors (pyrimidine dicarboxamides) that exhibit no detectable activity against other MMPs. The high-resolution X-ray structures of three molecules of this series bound to MMP-13 reveal a novel binding mode characterized by the absence of interactions between the inhibitors and the catalytic zinc. The inhibitors bind in the S1' pocket and extend into an additional S1' side pocket, which is unique to MMP-13. We analyze the determinants for selectivity and describe the rational design of improved compounds with low nanomolar affinity.
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__TOC__
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</StructureSection>
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==About this Structure==
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1XUC is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XUC OCA].
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==Reference==
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Structural basis for the highly selective inhibition of MMP-13., Engel CK, Pirard B, Schimanski S, Kirsch R, Habermann J, Klingler O, Schlotte V, Weithmann KU, Wendt KU, Chem Biol. 2005 Feb;12(2):181-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15734645 15734645]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Engel, C K.]]
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[[Category: Engel CK]]
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[[Category: Wendt, K U.]]
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[[Category: Wendt KU]]
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[[Category: CA]]
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[[Category: PB3]]
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[[Category: ZN]]
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[[Category: matrix metalloproteinase]]
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[[Category: non-zinc binding inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 14:16:14 2008''
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Current revision

Matrix metalloproteinase-13 complexed with non-zinc binding inhibitor

PDB ID 1xuc

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