3anr: Difference between revisions
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<StructureSection load='3anr' size='340' side='right'caption='[[3anr]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='3anr' size='340' side='right'caption='[[3anr]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3anr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3anr]] 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=3ANR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ANR FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HRM:7-METHOXY-1-METHYL-9H-BETA-CARBOLINE'>HRM</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=3anr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3anr OCA], [https://pdbe.org/3anr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3anr RCSB], [https://www.ebi.ac.uk/pdbsum/3anr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3anr 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=3anr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3anr OCA], [https://pdbe.org/3anr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3anr RCSB], [https://www.ebi.ac.uk/pdbsum/3anr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3anr 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 3anr" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3anr" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Hagiwara | [[Category: Hagiwara M]] | ||
[[Category: Hosoya | [[Category: Hosoya T]] | ||
[[Category: Ito | [[Category: Ito N]] | ||
[[Category: Nonaka | [[Category: Nonaka Y]] | ||
Latest revision as of 18:49, 4 October 2023
human DYRK1A/harmine complexhuman DYRK1A/harmine complex
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 (dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A) is a serine/threonine kinase essential for brain development and function, and its excessive activity is considered a pathogenic factor in Down syndrome. The development of potent, selective inhibitors of Dyrk1A would help to elucidate the molecular mechanisms of normal and diseased brains, and may provide a new lead compound for molecular-targeted drug discovery. Here, we report a novel Dyrk1A inhibitor, INDY, a benzothiazole derivative showing a potent ATP-competitive inhibitory effect with IC(50) and K(i) values of 0.24 and 0.18 muM, respectively. X-ray crystallography of the Dyrk1A/INDY complex revealed the binding of INDY in the ATP pocket of the enzyme. INDY effectively reversed the aberrant tau-phosphorylation and rescued the repressed NFAT (nuclear factor of activated T cell) signalling induced by Dyrk1A overexpression. Importantly, proINDY, a prodrug of INDY, effectively recovered Xenopus embryos from head malformation induced by Dyrk1A overexpression, resulting in normally developed embryos and demonstrating the utility of proINDY in vivo. Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A.,Ogawa Y, Nonaka Y, Goto T, Ohnishi E, Hiramatsu T, Kii I, Yoshida M, Ikura T, Onogi H, Shibuya H, Hosoya T, Ito N, Hagiwara M Nat Commun. 2010 Oct;1(7):1-9. PMID:20981014[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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