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5y86

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Revision as of 05:50, 30 May 2018

Crystal structure of kinase

Structural highlights

5y86 is a 1 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:	, ,
Gene:	DYRK3 (HUMAN)
Activity:	Dual-specificity kinase, with EC number 2.7.12.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DYRK3_HUMAN] Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Negative regulator of EPO-dependent erythropoiesis, may place an upper limit on red cell production during stress erythropoiesis. Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). May act by regulating CREB/CRE signaling (By similarity). Stabilizes and prevents stress granule disassembly thereby regulating mTORC1 signaling during cellular stress. During stressful conditions, DYRK3 partitions to the stress granule from the cytosol, as well as mTORC1 components, which prevents mTORC1 signaling. When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol, and promotes the phosphorylation of the mTORC1 inhibitor, AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1. This in turn inhibits TP53 activity and apoptosis (PubMed:20167603).[UniProtKB:Q922Y0]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Dual-specificity tyrosine-regulated kinases (DYRKs) auto-phosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues. The auto-phosphorylation occurs intramolecularly and is a one-off event. DYRK3 is selectively expressed at a high level in hematopoietic cells and attenuates erythroblast development, leading to anemia. In the present study, we determined the crystal structure of the mature form of human DYRK3 in complex with harmine, an ATP competitive inhibitor. The crystal structure revealed a phosphorylation site, residue S350, whose phosphorylation increases the stability of DYRK3 and enhances its kinase activity. In addition, our structural and biochemical assays suggest that the N-terminal auto-phosphorylation accessory domain stabilizes the DYRK3 protein, followed by auto-phosphorylation of the tyrosine of the activation loop, which is important for kinase activity. Finally, our docking analysis provides information for the design of novel and potent therapeutics to treat anemia.

Crystal Structure of Human Dual-Specificity Tyrosine-Regulated Kinase 3 Reveals New Structural Features and Insights into its Auto-phosphorylation.,Kim K, Cha JS, Cho YS, Kim H, Chang N, Kim HJ, Cho HS J Mol Biol. 2018 Apr 7. pii: S0022-2836(18)30189-X. doi:, 10.1016/j.jmb.2018.04.001. PMID:29634919^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lord KA, Creasy CL, King AG, King C, Burns BM, Lee JC, Dillon SB. REDK, a novel human regulatory erythroid kinase. Blood. 2000 May 1;95(9):2838-46. PMID:10779429
↑ Guo X, Williams JG, Schug TT, Li X. DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. J Biol Chem. 2010 Apr 23;285(17):13223-32. doi: 10.1074/jbc.M110.102574. Epub, 2010 Feb 18. PMID:20167603 doi:http://dx.doi.org/10.1074/jbc.M110.102574
↑ Wippich F, Bodenmiller B, Trajkovska MG, Wanka S, Aebersold R, Pelkmans L. Dual specificity kinase DYRK3 couples stress granule condensation/dissolution to mTORC1 signaling. Cell. 2013 Feb 14;152(4):791-805. doi: 10.1016/j.cell.2013.01.033. PMID:23415227 doi:http://dx.doi.org/10.1016/j.cell.2013.01.033
↑ Kim K, Cha JS, Cho YS, Kim H, Chang N, Kim HJ, Cho HS. Crystal Structure of Human Dual-Specificity Tyrosine-Regulated Kinase 3 Reveals New Structural Features and Insights into its Auto-phosphorylation. J Mol Biol. 2018 Apr 7. pii: S0022-2836(18)30189-X. doi:, 10.1016/j.jmb.2018.04.001. PMID:29634919 doi:http://dx.doi.org/10.1016/j.jmb.2018.04.001

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5y86"

@@ Line 3: / Line 3: @@
 <StructureSection load='5y86' size='340' side='right' caption='[[5y86]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5y86]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y86 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y86 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5y86]] is a 1 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=5Y86 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y86 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HRM:7-METHOXY-1-METHYL-9H-BETA-CARBOLINE'>HRM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DYRK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5y86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y86 OCA], [http://pdbe.org/5y86 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y86 RCSB], [http://www.ebi.ac.uk/pdbsum/5y86 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y86 ProSAT]</span></td></tr>
@@ Line 25: / Line 26: @@
 </StructureSection>
 [[Category: Dual-specificity kinase]]
+[[Category: Human]]
 [[Category: Cha, J S]]
 [[Category: Chang, N P]]

5y86

From Proteopedia

Revision as of 05:50, 30 May 2018

Crystal structure of kinase

Structural highlights

Function

Publication Abstract from PubMed

References

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