6eil: Difference between revisions
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<StructureSection load='6eil' size='340' side='right'caption='[[6eil]], [[Resolution|resolution]] 2.46Å' scene=''> | <StructureSection load='6eil' size='340' side='right'caption='[[6eil]], [[Resolution|resolution]] 2.46Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6eil]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[6eil]] is a 4 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=6EIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EIL FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B6B:[3-azanyl-6-(5-azanyl-2-methoxy-phenyl)pyrazin-2-yl]-pyridin-3-yl-methanone'>B6B</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.465Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B6B:[3-azanyl-6-(5-azanyl-2-methoxy-phenyl)pyrazin-2-yl]-pyridin-3-yl-methanone'>B6B</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=6eil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eil OCA], [https://pdbe.org/6eil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eil RCSB], [https://www.ebi.ac.uk/pdbsum/6eil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eil 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=6eil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eil OCA], [https://pdbe.org/6eil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eil RCSB], [https://www.ebi.ac.uk/pdbsum/6eil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eil ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
[https://www.uniprot.org/uniprot/DYR1A_HUMAN DYR1A_HUMAN] Defects in DYRK1A are the cause of mental retardation autosomal dominant type 7 (MRD7) [MIM:[https://omim.org/entry/614104 614104]. A disease characterized by primary microcephaly, severe mental retardation without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.<ref>PMID:21294719</ref> | |||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/DYR1A_HUMAN DYR1A_HUMAN] May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Phosphorylates serine, threonine and tyrosine residues in its sequence and in exogenous substrates.<ref>PMID:8769099</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6eil" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6eil" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Rothweiler | [[Category: Rothweiler U]] | ||
Latest revision as of 15:35, 6 November 2024
DYRK1A in complex with XMD8-49DYRK1A in complex with XMD8-49
Structural highlights
DiseaseDYR1A_HUMAN Defects in DYRK1A are the cause of mental retardation autosomal dominant type 7 (MRD7) [MIM:614104. A disease characterized by primary microcephaly, severe mental retardation without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.[1] FunctionDYR1A_HUMAN May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Phosphorylates serine, threonine and tyrosine residues in its sequence and in exogenous substrates.[2] Publication Abstract from PubMedDYRK1A is one of five members of the dual-specificity tyrosine (Y) phosphorylation-regulated kinase (DYRK) family. The DYRK1A gene is located in the Down syndrome critical region and regulates cellular processes related to proliferation and differentiation of neuronal progenitor cells during early development. This has focused research on its role in neuronal degenerative diseases, including Alzheimer's and Down syndrome. Recent studies have also shown a possible role of DYRK1A in diabetes. Here we report a variety of scaffolds not generally known for DYRK1A inhibition, demonstrating their effects in in vitro assays and also in cell cultures. These inhibitors effectively block the tau phosphorylation that is a hallmark of Alzheimer's disease. The crystal structures of these inhibitors support the design of optimized and novel therapeutics. Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase (DYRK1A) Inhibitors.,Czarna A, Wang J, Zelencova D, Liu Y, Deng X, Choi HG, Zhang T, Zhou W, Chang JW, Kildalsen H, Seternes OM, Gray NS, Engh RA, Rothweiler U J Med Chem. 2018 Aug 23. doi: 10.1021/acs.jmedchem.7b01847. PMID:30095246[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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