View source for 6vzk


==Crystal structure of human CaMKII-alpha (CAMK2A)kinase domain==
<StructureSection load='6vzk' size='340' side='right'caption='[[6vzk]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vzk]] 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=6VZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VZK 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]] 2.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HC4:4-HYDROXYCINNAMIC+ACID'>HC4</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=6vzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vzk OCA], [https://pdbe.org/6vzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vzk RCSB], [https://www.ebi.ac.uk/pdbsum/6vzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vzk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KCC2A_HUMAN KCC2A_HUMAN] CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release. Member of the NMDAR signaling complex in excitatory synapses it may regulate NMDAR-dependent potentiation of the AMPAR and synaptic plasticity (By similarity).
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== Publication Abstract from PubMed ==
Ca(2+) /calmodulin dependent protein kinase II (CaMKII) is a Ser/Thr kinase necessary for long-term memory formation and other Ca(2+) dependent signaling cascades such as fertilization. Here, we investigated the stability of CaMKIIalpha using a combination of differential scanning calorimetry (DSC), X-ray crystallography and Mass Photometry (MP). The kinase domain has a low thermal stability (apparent Tm = 36 degrees C), which is slightly stabilized by ATP/MgCl2 binding (apparent Tm = 40 degrees C), and significantly stabilized by regulatory segment binding (apparent Tm = 60 degrees C). We crystallized the kinase domain of CaMKII bound to p-coumaric acid in the active site. This structure reveals solvent-exposed hydrophobic residues in the substrate-binding pocket, which are normally buried in the autoinhibited structure when the regulatory segment is present. This likely accounts for the large stabilization we observe in DSC measurements comparing the kinase alone to the kinase plus regulatory segment. The hub domain alone is extremely stable (apparent Tm ~90 degrees C), and the holoenzyme structure has multiple unfolding transitions ranging from ~60 degrees C - 100 degrees C. Using MP, we compared a CaMKIIalpha holoenzyme with different variable linker regions and determined that the dissociation of both these holoenzymes occurs at a higher concentration (is less stable) compared to the hub domain alone. We conclude that within the context of the holoenzyme structure, the kinase domain is stabilized whereas the hub domain is destabilized. These data support a model where domains within the holoenzyme interact. This article is protected by copyright. All rights reserved.

Characterization of CaMKIIalpha holoenzyme stability.,Torres-Ocampo AP, Ozden C, Hommer A, Gardella A, Lapinskas E, Samkutty A, Esposito E, Garman S, Stratton M Protein Sci. 2020 Apr 13. doi: 10.1002/pro.3869. PMID:32282091<ref>PMID:32282091</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6vzk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Calcium/calmodulin dependent protein kinase 3D structures|Calcium/calmodulin dependent protein kinase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Garman SC]]
[[Category: Ozden C]]
[[Category: Stratton MM]]