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

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.

SUBMITTER: Lavogina D

PROVIDER: S-EPMC4854560 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Lavogina Darja D Kestav Katrin K Chaikuad Apirat A Heroven Christina C Knapp Stefan S Uri Asko A

Acta crystallographica. Section F, Structural biology communications 20160422 Pt 5

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 revealin ...[more]

PMID: 27139824

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