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4nct

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Revision as of 14:20, 27 April 2017

Human DYRK1A in complex with PKC412

Structural highlights

4nct is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:	,
Activity:	Dual-specificity kinase, with EC number 2.7.12.1
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

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a protein kinase associated with neuronal development and brain physiology. The DYRK kinases are very unusual with respect to the sequence of the catalytic loop, in which the otherwise highly conserved arginine of the HRD motif is replaced by a cysteine. This replacement, along with the proximity of a potential disulfide-bridge partner from the activation segment, implies a potential for redox control of DYRK family activities. Here, the crystal structure of DYRK1A bound to PKC412 is reported, showing the formation of the disulfide bridge and associated conformational changes of the activation loop. The DYRK kinases represent emerging drug targets for several neurological diseases as well as cancer. The observation of distinct activation states may impact strategies for drug targeting. In addition, the characterization of PKC412 binding offers new insights for DYRK inhibitor discovery.

The structure of a dual-specificity tyrosine phosphorylation-regulated kinase 1A-PKC412 complex reveals disulfide-bridge formation with the anomalous catalytic loop HRD(HCD) cysteine.,Alexeeva M, Aberg E, Engh RA, Rothweiler U Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1207-15. doi:, 10.1107/S1399004715005106. Epub 2015 Apr 25. PMID:25945585^[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
↑ Alexeeva M, Aberg E, Engh RA, Rothweiler U. The structure of a dual-specificity tyrosine phosphorylation-regulated kinase 1A-PKC412 complex reveals disulfide-bridge formation with the anomalous catalytic loop HRD(HCD) cysteine. Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1207-15. doi:, 10.1107/S1399004715005106. Epub 2015 Apr 25. PMID:25945585 doi:http://dx.doi.org/10.1107/S1399004715005106

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4nct"

Categories: Dual-specificity kinase | Alexeeva, M O | Rothweiler, U | Protein kinase | Transferase-transferase inhibitor complex

@@ Line 1: / Line 1: @@
 ==Human DYRK1A in complex with PKC412==
 <StructureSection load='4nct' size='340' side='right' caption='[[4nct]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <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>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></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=4nct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nct OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nct RCSB], [http://www.ebi.ac.uk/pdbsum/4nct PDBsum]</span></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=4nct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nct OCA], [http://pdbe.org/4nct PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nct RCSB], [http://www.ebi.ac.uk/pdbsum/4nct PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nct ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4nct" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4nct

From Proteopedia

Revision as of 14:20, 27 April 2017

Human DYRK1A in complex with PKC412

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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