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

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.

Source: Acta Crystallographica Section F - April 21, 2016 Category: Biochemistry Authors: Lavogina, D.Kestav, K.Chaikuad, A.Heroven, C.Knapp, S.Uri, A. Tags: protein kinase haspin histone inhibitor bisubstrate linker research communications Source Type: research