6eil

From Proteopedia

(Difference between revisions)

Revision as of 09:10, 11 November 2020

DYRK1A in complex with XMD8-49

Structural highlights

6eil is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[DYR1A_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]

Function

[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.^[2]

Publication Abstract from PubMed

DYRK1A 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

↑ van Bon BW, Hoischen A, Hehir-Kwa J, de Brouwer AP, Ruivenkamp C, Gijsbers AC, Marcelis CL, de Leeuw N, Veltman JA, Brunner HG, de Vries BB. Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly. Clin Genet. 2011 Mar;79(3):296-9. doi: 10.1111/j.1399-0004.2010.01544.x. PMID:21294719 doi:10.1111/j.1399-0004.2010.01544.x
↑ Shindoh N, Kudoh J, Maeda H, Yamaki A, Minoshima S, Shimizu Y, Shimizu N. Cloning of a human homolog of the Drosophila minibrain/rat Dyrk gene from "the Down syndrome critical region" of chromosome 21. Biochem Biophys Res Commun. 1996 Aug 5;225(1):92-9. PMID:8769099 doi:S0006-291X(96)91135-3
↑ 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. Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase (DYRK1A) Inhibitors. J Med Chem. 2018 Aug 23. doi: 10.1021/acs.jmedchem.7b01847. PMID:30095246 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b01847

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6eil"

Categories: Human | Large Structures | Rothweiler, U | Dual specificity tyrosine-phosphorylation-regulated kinase 1a | Transferase

@@ Line 1: / Line 1: @@
 ==DYRK1A in complex with XMD8-49==
-<StructureSection load='6eil' size='340' side='right' caption='[[6eil]], [[Resolution|resolution]] 2.46&Aring;' scene=''>
+<StructureSection load='6eil' size='340' side='right'caption='[[6eil]], [[Resolution|resolution]] 2.46&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6eil]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EIL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6eil]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://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"><scene name='pdbligand=B6B:[3-azanyl-6-(5-azanyl-2-methoxy-phenyl)pyrazin-2-yl]-pyridin-3-yl-methanone'>B6B</scene></td></tr>
+</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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6eil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eil OCA], [http://pdbe.org/6eil PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eil RCSB], [http://www.ebi.ac.uk/pdbsum/6eil PDBsum], [http://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'>[http://proteopedia.org/fgij/fg.htm?mol=6eil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eil OCA], [http://pdbe.org/6eil PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eil RCSB], [http://www.ebi.ac.uk/pdbsum/6eil PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eil ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 21: @@
 </div>
 <div class="pdbe-citations 6eil" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dual specificity tyrosine-phosphorylation-regulated kinase|Dual specificity tyrosine-phosphorylation-regulated kinase]]
 == References ==
 <references/>
@@ Line 26: / Line 29: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Rothweiler, U]]
 [[Category: Dual specificity tyrosine-phosphorylation-regulated kinase 1a]]
 [[Category: Transferase]]

6eil

From Proteopedia

Revision as of 09:10, 11 November 2020

DYRK1A in complex with XMD8-49

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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