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

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.

SUBMITTER: Burgess SG

PROVIDER: S-EPMC4356308 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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

Burgess Selena G SG Bayliss Richard R

Acta crystallographica. Section F, Structural biology communications 20150219 Pt 3

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 ...[more]

PMID: 25760707

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