Rxivist logo

Aurora A is a cell cycle protein kinase implicated in multiple human cancers, and several Aurora A-specific kinase inhibitors have progressed into clinical trials. In this study, we report structural and cellular analysis of a novel biochemical mode of Aurora A inhibition, which occurs through reversible covalent interaction with the universal metabolic integrator coenzyme A (CoA). Mechanistically, the CoA 3'-phospho ADP moiety interacts with Thr 217, an Aurora A selectivity filter, which permits the formation of an unprecedented covalent bond with Cys 290 in the kinase activation segment, lying some 15 A away. CoA modification (CoAlation) of endogenous Aurora A is rapidly induced by oxidative stresses at Cys 290 in human cells, and microinjection of CoA into mouse embryos perturbs meitoic spindle formation and chromosome alignment. Aurora A regulation by CoA reveals how targeting of Aurora A might be accomplished in the future by development of a 'double-anchored' covalent inhibitor.

Download data

  • Downloaded 554 times
  • Download rankings, all-time:
    • Site-wide: 48,434
    • In biochemistry: 1,259
  • Year to date:
    • Site-wide: 63,370
  • Since beginning of last month:
    • Site-wide: 58,394

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

News