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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.

Author information

1
Institute of Chemistry, University of Tartu, Ravila 14A, 50411 Tartu, Estonia.
2
Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, England.

Abstract

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.

KEYWORDS:

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

PMID:
27139824
PMCID:
PMC4854560
DOI:
10.1107/S2053230X16004611
[Indexed for MEDLINE]
Free PMC Article

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