4pdp: Difference between revisions

Latest revision as of 07:15, 27 September 2023

Crystal structure of Rad53 kinase domain and SCD2

Structural highlights

4pdp is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.591Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

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

References

↑ Zheng P, Fay DS, Burton J, Xiao H, Pinkham JL, Stern DF. SPK1 is an essential S-phase-specific gene of Saccharomyces cerevisiae that encodes a nuclear serine/threonine/tyrosine kinase. Mol Cell Biol. 1993 Sep;13(9):5829-42. PMID:8355715
↑ Allen JB, Zhou Z, Siede W, Friedberg EC, Elledge SJ. The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. Genes Dev. 1994 Oct 15;8(20):2401-15. PMID:7958905
↑ Sanchez Y, Bachant J, Wang H, Hu F, Liu D, Tetzlaff M, Elledge SJ. Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science. 1999 Nov 5;286(5442):1166-71. PMID:10550056
↑ Kim EM, Jang YK, Park SD. Phosphorylation of Rph1, a damage-responsive repressor of PHR1 in Saccharomyces cerevisiae, is dependent upon Rad53 kinase. Nucleic Acids Res. 2002 Feb 1;30(3):643-8. PMID:11809875
↑ Pike BL, Yongkiettrakul S, Tsai MD, Heierhorst J. Mdt1, a novel Rad53 FHA1 domain-interacting protein, modulates DNA damage tolerance and G(2)/M cell cycle progression in Saccharomyces cerevisiae. Mol Cell Biol. 2004 Apr;24(7):2779-88. PMID:15024067
↑ Wybenga-Groot LE, Ho CS, Sweeney FD, Ceccarelli DF, Jane McGlade C, Durocher D, Sicheri F. Structural basis of Rad53 kinase activation by dimerization and activation segment exchange. Cell Signal. 2014 May 9. pii: S0898-6568(14)00174-0. doi:, 10.1016/j.cellsig.2014.05.004. PMID:24815189 doi:https://dx.doi.org/10.1016/j.cellsig.2014.05.004

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Zheng P, Fay DS, Burton J, Xiao H, Pinkham JL, Stern DF. SPK1 is an essential S-phase-specific gene of Saccharomyces cerevisiae that encodes a nuclear serine/threonine/tyrosine kinase. Mol Cell Biol. 1993 Sep;13(9):5829-42. PMID:8355715

[2] Allen JB, Zhou Z, Siede W, Friedberg EC, Elledge SJ. The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. Genes Dev. 1994 Oct 15;8(20):2401-15. PMID:7958905

[3] Sanchez Y, Bachant J, Wang H, Hu F, Liu D, Tetzlaff M, Elledge SJ. Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science. 1999 Nov 5;286(5442):1166-71. PMID:10550056

[4] Kim EM, Jang YK, Park SD. Phosphorylation of Rph1, a damage-responsive repressor of PHR1 in Saccharomyces cerevisiae, is dependent upon Rad53 kinase. Nucleic Acids Res. 2002 Feb 1;30(3):643-8. PMID:11809875

[5] Pike BL, Yongkiettrakul S, Tsai MD, Heierhorst J. Mdt1, a novel Rad53 FHA1 domain-interacting protein, modulates DNA damage tolerance and G(2)/M cell cycle progression in Saccharomyces cerevisiae. Mol Cell Biol. 2004 Apr;24(7):2779-88. PMID:15024067

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

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@@ Line 1: / Line 1: @@
 ==Crystal structure of Rad53 kinase domain and SCD2==
-<StructureSection load='4pdp' size='340' side='right' caption='[[4pdp]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
+<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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PDP FirstGlance]. <br>
+<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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pds|4pds]]</td></tr>
+</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='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'>[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>
-<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=4pdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pdp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pdp RCSB], [http://www.ebi.ac.uk/pdbsum/4pdp PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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 ==
@@ Line 17: / Line 17: @@
 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==
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Dual-specificity kinase]]
+[[Category: Large Structures]]
-[[Category: Ceccarelli, D F]]
+[[Category: Saccharomyces cerevisiae]]
-[[Category: Ho, C S]]
+[[Category: Ceccarelli DF]]
-[[Category: Sicheri, F]]
+[[Category: Ho CS]]
-[[Category: Wybenga-Groot, L E]]
+[[Category: Sicheri F]]
-[[Category: Activation segment exchange]]
+[[Category: Wybenga-Groot LE]]
-[[Category: C-lobe]]
-[[Category: N-lobe]]
-[[Category: Ser/thr kinase domain]]
-[[Category: Transferase]]

4pdp: Difference between revisions

Latest revision as of 07:15, 27 September 2023

Crystal structure of Rad53 kinase domain and SCD2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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