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The structure of C290A:C393A Aurora A provides structural insights into kinase regulation
Author(s) -
Burgess Selena G.,
Bayliss Richard
Publication year - 2015
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x15002290
Subject(s) - autophosphorylation , protein kinase domain , chemistry , microbiology and biotechnology , mutant , threonine , kinase , mitosis , phosphorylation , transferase , biochemistry , protein kinase a , biology , serine , enzyme , gene
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.