View source for 4pdp


==Crystal structure of Rad53 kinase domain and SCD2==
<StructureSection load='4pdp' size='340' side='right'caption='[[4pdp]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4pdp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PDP 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]] 2.591&#8491;</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=4pdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pdp OCA], [https://pdbe.org/4pdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pdp RCSB], [https://www.ebi.ac.uk/pdbsum/4pdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pdp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RAD53_YEAST RAD53_YEAST] Controls S-phase checkpoint as well as G1 and G2 DNA damage checkpoints. Phosphorylates proteins on serine, threonine, and tyrosine. Prevents entry into anaphase and mitotic exit after DNA damage via regulation of the Polo kinase CDC5. Seems to be involved in the phosphorylation of RPH1.<ref>PMID:8355715</ref> <ref>PMID:7958905</ref> <ref>PMID:10550056</ref> <ref>PMID:11809875</ref> <ref>PMID:15024067</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The protein kinase Rad53 is a key regulator of the DNA damage checkpoint in budding yeast. Its human ortholog, CHEK2, is mutated in familial breast cancer and mediates apoptosis in response to genotoxic stress. Autophosphorylation of Rad53 at residue Thr354 located in the kinase activation segment is essential for Rad53 activation. In this study, we assessed the requirement of kinase domain dimerization and the exchange of its activation segment during the Rad53 activation process. We solved the crystal structure of Rad53 in its dimeric form and found that disruption of the observed head-to-tail, face-to-face dimer structure decreased Rad53 autophosphorylation on Thr354 in vitro and impaired Rad53 function in vivo. Moreover, we provide critical functional evidence that Rad53 trans-autophosphorylation may involve the interkinase domain exchange of helix alphaEF via an invariant salt bridge. These findings suggest a mechanism of autophosphorylation that may be broadly applicable to other protein kinases.

Structural basis of Rad53 kinase activation by dimerization and activation segment exchange.,Wybenga-Groot LE, Ho CS, Sweeney FD, Ceccarelli DF, Jane McGlade C, Durocher D, Sicheri F Cell Signal. 2014 May 9. pii: S0898-6568(14)00174-0. doi:, 10.1016/j.cellsig.2014.05.004. PMID:24815189<ref>PMID:24815189</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4pdp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Protein kinase Spk1|Protein kinase Spk1]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Ceccarelli DF]]
[[Category: Ho CS]]
[[Category: Sicheri F]]
[[Category: Wybenga-Groot LE]]