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Updated: Mar 21, 2026

Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
Co-crystal structures of the protein kinase haspin with bisubstrate inhibitors
Darja Lavogina1, Katrin Kestav1, Apirat Chaikuad2
1Institute of Chemistry, University of Tartu, Ravila 14A, 50411 Tartu, Estonia.
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.
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