View source for 2ya9


==Crystal structure of the autoinhibited form of mouse DAPK2==
<StructureSection load='2ya9' size='340' side='right'caption='[[2ya9]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ya9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YA9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YA9 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=D1D:(4S,5S)-1,2-DITHIANE-4,5-DIOL'>D1D</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=2ya9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ya9 OCA], [https://pdbe.org/2ya9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ya9 RCSB], [https://www.ebi.ac.uk/pdbsum/2ya9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ya9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DAPK2_MOUSE DAPK2_MOUSE] Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Capable of regulating both type I apoptotic and type II autophagic cell deaths signal. The former involves caspase activation, chromatin and mitochondrial condensation while the latter involves caspase-independent cell death in conjunction with accumulation of mature autophagic vesicles, plasma membrane blebs, and nuclear condensation without DNA degradation. Mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (By similarity).[UniProtKB:P53355][UniProtKB:Q9UIK4]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The death-associated protein kinase (DAPK) family has been characterized as a group of pro-apoptotic serine/threonine kinases that share specific structural features in their catalytic kinase domain. Two of the DAPK family members, DAPK1 and DAPK2, are calmodulin-dependent protein kinases that are regulated by oligomerization, calmodulin binding, and autophosphorylation. In this study, we have determined the crystal and solution structures of murine DAPK2 in the presence of the autoinhibitory domain, with and without bound nucleotides in the active site. The crystal structure shows dimers of DAPK2 in a conformation that is not permissible for protein substrate binding. Two different conformations were seen in the active site upon the introduction of nucleotide ligands. The monomeric and dimeric forms of DAPK2 were further analyzed for solution structure, and the results indicate that the dimers of DAPK2 are indeed formed through the association of two apposed catalytic domains, as seen in the crystal structure. The structures can be further used to build a model for DAPK2 autophosphorylation and to compare with closely related kinases, of which especially DAPK1 is an actively studied drug target. Our structures also provide a model for both homodimerization and heterodimerization of the catalytic domain between members of the DAPK family. The fingerprint of the DAPK family, the basic loop, plays a central role in the dimerization of the kinase domain.

Structure of the Dimeric Autoinhibited Conformation of DAPK2, a Pro-Apoptotic Protein Kinase.,Patel AK, Yadav RP, Majava V, Kursula I, Kursula P J Mol Biol. 2011 Apr 8. PMID:21497605<ref>PMID:21497605</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2ya9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Death-associated protein kinase 3D structures|Death-associated protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Kursula P]]
[[Category: Patel AK]]