View source for 2xuu


==Crystal structure of a DAP-kinase 1 mutant==
<StructureSection load='2xuu' size='340' side='right'caption='[[2xuu]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2xuu]] is a 1 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=2XUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XUU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2xuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xuu OCA], [https://pdbe.org/2xuu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xuu RCSB], [https://www.ebi.ac.uk/pdbsum/2xuu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xuu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DAPK1_HUMAN DAPK1_HUMAN] Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.<ref>PMID:7828849</ref> <ref>PMID:10629061</ref> <ref>PMID:11579085</ref> <ref>PMID:11980920</ref> <ref>PMID:12730201</ref> <ref>PMID:15367680</ref> <ref>PMID:17703233</ref> <ref>PMID:17895359</ref> <ref>PMID:18422656</ref> <ref>PMID:18195017</ref> <ref>PMID:18995835</ref> <ref>PMID:19180116</ref> <ref>PMID:18974095</ref> <ref>PMID:21497122</ref> <ref>PMID:21408167</ref>   Isoform 2 cannot induce apoptosis but can induce membrane blebbing.<ref>PMID:7828849</ref> <ref>PMID:10629061</ref> <ref>PMID:11579085</ref> <ref>PMID:11980920</ref> <ref>PMID:12730201</ref> <ref>PMID:15367680</ref> <ref>PMID:17703233</ref> <ref>PMID:17895359</ref> <ref>PMID:18422656</ref> <ref>PMID:18195017</ref> <ref>PMID:18995835</ref> <ref>PMID:19180116</ref> <ref>PMID:18974095</ref> <ref>PMID:21497122</ref> <ref>PMID:21408167</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Knowledge about protein kinase substrate preferences is biased toward residues immediately adjacent to the site of phosphorylation. By a combined structural, biochemical, and cellular approach, we have discovered an unexpected substrate recognition element with the consensus sequence PEF/Y in the tumor suppressor death-associated protein kinase 1. This motif can be effectively blocked by a specific pseudosubstrate-type interaction with an autoregulatory domain of this kinase. In this arrangement, the central PEF/Y glutamate interacts with a conserved arginine distant to the phosphorylation site in sequence and structure. We also demonstrate that the element is crucial for kinase activity regulation and substrate recognition. The PEF/Y motif distinguishes close death-associated protein kinase relatives from canonical calcium/calmodulin-dependent protein kinases. Insight into this signature and mode of action offers new opportunities to identify specific small molecule inhibitors in PEF/Y-containing protein kinases.

A PEF/Y Substrate Recognition and Signature Motif Plays a Critical Role in DAPK-Related Kinase Activity.,Temmerman K, de Diego I, Pogenberg V, Simon B, Jonko W, Li X, Wilmanns M Chem Biol. 2014 Jan 14. pii: S1074-5521(13)00457-2. doi:, 10.1016/j.chembiol.2013.12.008. PMID:24440081<ref>PMID:24440081</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2xuu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Death-associated protein kinase 3D structures|Death-associated protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kuper J]]
[[Category: Lehmann F]]
[[Category: Wilmanns M]]
[[Category: De Diego I]]