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Structure of Aurora B-INCENP in complex with barasertib reveals a potential transinhibitory mechanism.

ABSTRACT: The Aurora family is a well conserved and well characterized group of serine-threonine kinases involved in the normal progression of mitosis. The deregulation of Aurora kinases impairs spindle assembly, checkpoint function and cell division. To date, many small molecules that compete with ATP for binding to Aurora kinases have been developed and characterized. Here, the first structure of the Xenopus laevis Aurora B-INCENP complex bound to the clinically relevant small molecule barasertib was determined. The binding properties of this inhibitor to the Aurora B active site are analyzed and reported. An unexpected crystal-packing contact in the Aurora B-INCENP structure coordinated by an ATP analogue is also reported, in which the INCENP C-terminus occupies the substrate-binding region, resembling the protein kinase A inhibitory mechanism.

SUBMITTER: Sessa F

PROVIDER: S-EPMC3944688 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Structure of Aurora B-INCENP in complex with barasertib reveals a potential transinhibitory mechanism.

Sessa Fabio F Villa Fabrizio F

Acta crystallographica. Section F, Structural biology communications 20140219 Pt 3

The Aurora family is a well conserved and well characterized group of serine-threonine kinases involved in the normal progression of mitosis. The deregulation of Aurora kinases impairs spindle assembly, checkpoint function and cell division. To date, many small molecules that compete with ATP for binding to Aurora kinases have been developed and characterized. Here, the first structure of the Xenopus laevis Aurora B-INCENP complex bound to the clinically relevant small molecule barasertib was de ...[more]

PMID: 24598913

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Crystal structure of human aurora B in complex with INCENP and VX-680.

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