3kec

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Current revision (08:45, 7 February 2024) (edit) (undo)
 
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<StructureSection load='3kec' size='340' side='right'caption='[[3kec]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
<StructureSection load='3kec' size='340' side='right'caption='[[3kec]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3kec]] is a 2 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=3KEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KEC FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3kec]] 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=3KEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KEC FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3KE:4-{[({3-[2-(4-METHOXYBENZYL)-2H-TETRAZOL-5-YL]PHENYL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>3KE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HAE:ACETOHYDROXAMIC+ACID'>HAE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.05&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3kej|3kej]], [[3kek|3kek]]</div></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=3KE:4-{[({3-[2-(4-METHOXYBENZYL)-2H-TETRAZOL-5-YL]PHENYL}CARBONYL)AMINO]METHYL}BENZOIC+ACID'>3KE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HAE:ACETOHYDROXAMIC+ACID'>HAE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<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>
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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=3kec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kec OCA], [https://pdbe.org/3kec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kec RCSB], [https://www.ebi.ac.uk/pdbsum/3kec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kec 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=3kec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kec OCA], [https://pdbe.org/3kec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kec RCSB], [https://www.ebi.ac.uk/pdbsum/3kec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kec ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== 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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[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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[[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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[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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Potent, highly selective and orally-bioavailable MMP-13 inhibitors have been identified based upon a (pyridin-4-yl)-2H-tetrazole scaffold. Co-crystal structure analysis revealed that the inhibitors bind at the S(1)(') active site pocket and are not ligands for the catalytic zinc atom. Compound 29b demonstrated reduction of cartilage degradation biomarker (TIINE) levels associated with cartilage protection in a preclinical rat osteoarthritis model.
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Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis.,Schnute ME, O'Brien PM, Nahra J, Morris M, Howard Roark W, Hanau CE, Ruminski PG, Scholten JA, Fletcher TR, Hamper BC, Carroll JN, Patt WC, Shieh HS, Collins B, Pavlovsky AG, Palmquist KE, Aston KW, Hitchcock J, Rogers MD, McDonald J, Johnson AR, Munie GE, Wittwer AJ, Man CF, Settle SL, Nemirovskiy O, Vickery LE, Agawal A, Dyer RD, Sunyer T Bioorg Med Chem Lett. 2010 Jan 15;20(2):576-80. Epub 2009 Nov 22. PMID:20005097<ref>PMID:20005097</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3kec" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Collins, B]]
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[[Category: Collins B]]
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[[Category: Pavlovsky, A G]]
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[[Category: Pavlovsky AG]]
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[[Category: Schnute, M E]]
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[[Category: Schnute ME]]
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[[Category: Shieh, H S]]
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[[Category: Shieh H-S]]
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[[Category: Collagen degradation]]
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[[Category: Disease mutation]]
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[[Category: Disulfide bond]]
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[[Category: Extracellular matrix]]
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[[Category: Glycoprotein]]
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[[Category: Hydrolase]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Metal-binding]]
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[[Category: Metalloprotease]]
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[[Category: No contact to zn]]
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[[Category: Protease]]
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[[Category: S1' inhibitor]]
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[[Category: S1' specificity pocket]]
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[[Category: Secreted]]
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[[Category: Selective mmp-13 inhibitor]]
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[[Category: Zymogen]]
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Current revision

Crystal Structure of Human MMP-13 complexed with a phenyl-2H-tetrazole compound

PDB ID 3kec

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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