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The structure of C290A: C393A Aurora A provides structural insights into kinase regulation

DOI: 10.1107/S2053230X15002290 DOI Help
PMID: 25760707 PMID Help

Authors: Selena Burgess (University of Leicester) , Richard Bayliss (University of Leicester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section F Structural Biology Communications , VOL 71 , PAGES 315 - 319

State: Published (Approved)
Published: March 2015
Diamond Proposal Number(s): 10369

Abstract: Aurora A is a Ser/Thr protein kinase that functions in cell-cycle regulation and is implicated in cancer development. During mitosis, Aurora A is activated by autophosphorylation on its activation loop at Thr288. The Aurora A catalytic domain (amino acids 122-403) expressed in Escherichia coli autophosphorylates on two activation-loop threonine residues (Thr288 and Thr287), whereas a C290A,C393A double point mutant of the Aurora A catalytic domain autophosphorylates only on Thr288. The structure of the complex of this mutant with ADP and magnesium was determined to 2.1 Å resolution using molecular replacement. This is an improvement on the existing 2.75 Å resolution structure of the equivalent wild-type complex. The structure confirms that single phosphorylation of the activation loop on Thr288 is insufficient to stabilize a `fully active' conformation of the activation loop in the absence of binding to TPX2.

Journal Keywords: Protein Kinase; Phosphorylation; Activation

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)