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1ztq

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Revision as of 09:24, 2 May 2018

Crystal structure of the catalytic domain of MMP-13 complexed with WAY-033

Structural highlights

1ztq is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	MMP13 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 potent, selective series of MMP-13 inhibitors has been derived from a weak (3.2 microM) inhibitor that did not bear a zinc chelator. Structure-based drug design strategies were employed to append a Zn-chelating group to one end of the molecule and functionality to enhance selectivity to the other. A compound from this series demonstrated rat oral bioavailability and efficacy in a bovine articular cartilage explant model.

Identification of potent and selective MMP-13 inhibitors.,Wu J, Rush TS 3rd, Hotchandani R, Du X, Geck M, Collins E, Xu ZB, Skotnicki J, Levin JI, Lovering FE Bioorg Med Chem Lett. 2005 Sep 15;15(18):4105-9. PMID:16005220^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Wu J, Rush TS 3rd, Hotchandani R, Du X, Geck M, Collins E, Xu ZB, Skotnicki J, Levin JI, Lovering FE. Identification of potent and selective MMP-13 inhibitors. Bioorg Med Chem Lett. 2005 Sep 15;15(18):4105-9. PMID:16005220 doi:http://dx.doi.org/10.1016/j.bmcl.2005.06.019

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1ztq"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the catalytic domain of MMP-13 complexed with WAY-033==
 <StructureSection load='1ztq' size='340' side='right' caption='[[1ztq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=033:N-({4-[(1-BENZOFURAN-2-YLCARBONYL)AMINO]-1,1-BIPHENYL-4-YL}SULFONYL)-L-VALINE'>033</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 ([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=1ztq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ztq OCA], [http://pdbe.org/1ztq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ztq RCSB], [http://www.ebi.ac.uk/pdbsum/1ztq 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=1ztq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ztq OCA], [http://pdbe.org/1ztq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ztq RCSB], [http://www.ebi.ac.uk/pdbsum/1ztq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ztq ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zt/1ztq_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zt/1ztq_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 1ztq" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Matrix metalloproteinase|Matrix metalloproteinase]]
 == References ==
 <references/>
@@ Line 50: / Line 48: @@
 [[Category: Collagenase]]
 [[Category: Hydrolase]]
-[[Category: Hydrophobic s1s']]
+[[Category: Hydrophobic s1ss']]
 [[Category: Hydroxamate]]
 [[Category: Metalloprotease]]
-[[Category: Mmp-13]]
 [[Category: Mmp]]
+[[Category: Mmp-13]]
 [[Category: P1' group]]
 [[Category: Zinc chelator]]

1ztq

From Proteopedia

Revision as of 09:24, 2 May 2018

Crystal structure of the catalytic domain of MMP-13 complexed with WAY-033

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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