3anq

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[[Image:3anq.png|left|200px]]
 
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{{STRUCTURE_3anq| PDB=3anq | SCENE= }}
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==human DYRK1A/inhibitor complex==
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<StructureSection load='3anq' size='340' side='right'caption='[[3anq]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3anq]] 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=3ANQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ANQ FirstGlance]. <br>
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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]] 2.6&#8491;</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=EHB:(1Z)-1-(3-ETHYL-5-HYDROXY-1,3-BENZOTHIAZOL-2(3H)-YLIDENE)PROPAN-2-ONE'>EHB</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=3anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3anq OCA], [https://pdbe.org/3anq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3anq RCSB], [https://www.ebi.ac.uk/pdbsum/3anq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3anq ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Dyrk1A (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.
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===human DYRK1A/inhibitor complex===
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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<ref>PMID:20981014</ref>
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{{ABSTRACT_PUBMED_20981014}}
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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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==About this Structure==
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<div class="pdbe-citations 3anq" style="background-color:#fffaf0;"></div>
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[[3anq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ANQ OCA].
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== References ==
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<references/>
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==Reference==
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__TOC__
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<ref group="xtra">PMID:020981014</ref><references group="xtra"/>
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</StructureSection>
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[[Category: Dual-specificity kinase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hagiwara, M.]]
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[[Category: Large Structures]]
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[[Category: Hosoya, T.]]
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[[Category: Hagiwara M]]
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[[Category: Ito, N.]]
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[[Category: Hosoya T]]
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[[Category: Nonaka, Y.]]
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[[Category: Ito N]]
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[[Category: Protein kinase]]
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[[Category: Nonaka Y]]
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[[Category: Transferase]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

human DYRK1A/inhibitor complex

PDB ID 3anq

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