View source for 6fer


==Crystal Structure of human DDR2 kinase in complex with 2-[4,5-difluoro-2-oxo-1'-(1H-pyrazolo[3,4-b]pyridine-5-carbonyl)spiro[indole-3,4'-piperidine]-1-yl]-N-(2,2,2-trifluoroethyl)acetamide==
<StructureSection load='6fer' size='340' side='right'caption='[[6fer]], [[Resolution|resolution]] 2.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fer]] is a 12 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=6FER OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FER FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.87&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D6Q:2-[4,5-bis(fluoranyl)-2-oxidanylidene-1-(1~{H}-pyrazolo[3,4-b]pyridin-5-ylcarbonyl)spiro[indole-3,4-piperidine]-1-yl]-~{N}-[2,2,2-tris(fluoranyl)ethyl]ethanamide'>D6Q</scene></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=6fer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fer OCA], [https://pdbe.org/6fer PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fer RCSB], [https://www.ebi.ac.uk/pdbsum/6fer PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fer ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/DDR2_HUMAN DDR2_HUMAN] Defects in DDR2 are the cause of spondyloepimetaphyseal dysplasia short limb-hand type (SEMD-SL) [MIM:[https://omim.org/entry/271665 271665]. A bone disease characterized by short-limbed dwarfism, a narrow chest with pectus excavatum, brachydactyly in the hands and feet, a characteristic craniofacial appearance and premature calcifications. The radiological findings are distinctive and comprise short long bones throughout the skeleton with striking epiphyses that are stippled, flattened and fragmented and flared, irregular metaphyses. Platyspondyly in the spine with wide intervertebral spaces is observed and some vertebral bodies are pear-shaped with central humps, anterior protrusions and posterior scalloping.<ref>PMID:20223752</ref> <ref>PMID:19110212</ref> 
== Function ==
[https://www.uniprot.org/uniprot/DDR2_HUMAN DDR2_HUMAN] Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing.<ref>PMID:9659899</ref> <ref>PMID:16186108</ref> <ref>PMID:16186104</ref> <ref>PMID:17665456</ref> <ref>PMID:18201965</ref> <ref>PMID:20564243</ref> <ref>PMID:20734453</ref> <ref>PMID:20004161</ref> 

==See Also==
*[[Epithelial discoidin domain-containing receptor|Epithelial discoidin domain-containing receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Benz J]]
[[Category: Kuhn B]]
[[Category: Richter H]]
[[Category: Rudolph MG]]
[[Category: Stihle M]]