title: Substrate specificity of protein kinases and computational prediction of substrates.
abstract: To ensure signalling fidelity, kinases must act only on a defined subset of cellular targets. Appreciating the basis for this substrate specificity is essential for understanding the role of an individual protein kinase in a particular cellular process. The specificity in the cell is determined by a combination of "peptide specificity" of the kinase (the molecular recognition of the sequence surrounding the phosphorylation site), substrate recruitment and phosphatase activity. Peptide specificity plays a crucial role and depends on the complementarity between the kinase and the substrate and therefore on their three-dimensional structures. Methods for experimental identification of kinase substrates and characterization of specificity are expensive and laborious, therefore, computational approaches are being developed to reduce the amount of experimental work required in substrate identification. We discuss the structural basis of substrate specificity of protein kinases and review the experimental and computational methods used to obtain specificity information.
authors.affiliation: School of Molecular and Microbial Sciences, University of Queensland, Brisbane, Australia. b.kobe@uq.edu.au
authors.forename: Bostjan
authors.initials: B
authors.lastname: Kobe
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kampmann
authors.forename: Jade K
authors.initials: JK
authors.lastname: Forwood
authors.forename: Pawel
authors.initials: P
authors.lastname: Listwan
authors.forename: Ross I
authors.initials: RI
authors.lastname: Brinkworth
mesh_terms: D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D013379:Substrate Specificity
chemical_list: D010455:Peptides; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases