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Acta Crystallogr F Struct Biol Commun. 2016 May;72(Pt 5):339-45. doi: 10.1107/S2053230X16004611. Epub 2016 Apr 22.

Co-crystal structures of the protein kinase haspin with bisubstrate inhibitors.

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Institute of Chemistry, University of Tartu, Ravila 14A, 50411 Tartu, Estonia.
Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, England.


Haspin is a mitotic protein kinase that is responsible for the phosphorylation of Thr3 of histone H3, thereby creating a recognition motif for docking of the chromosomal passenger complex that is crucial for the progression of cell division. Here, two high-resolution models of haspin with previously reported inhibitors consisting of an ATP analogue and a histone H3(1-7) peptide analogue are presented. The structures of the complexes confirm the bisubstrate character of the inhibitors by revealing the signature binding modes of the moieties targeting the ATP-binding site and the protein substrate-binding site of the kinase. This is the first structural model of a bisubstrate inhibitor targeting haspin. The presented structural data represent a model for the future development of more specific haspin inhibitors.


bisubstrate; haspin; histone; inhibitor; linker; protein kinase

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