title: Occupational hazards: allosteric regulation of protein kinases through the nucleotide-binding pocket.
abstract: Targeting the protein kinase ATP-binding pocket provides a significant opportunity for the treatment of disease. Recent studies have revealed a central activity-independent role for nucleotide pocket occupation in the allosteric behaviour of diverse kinases. Regulation of nucleotide pocket conformation with either nucleotides or ATP competitive inhibitors has revealed an added dimension to the targeting of kinases. In the present paper, using PKC (protein kinase C) as a paradigm, the liabilities and opportunities associated with the occupation of the nucleotide pocket are explored.
authors.affiliation: Cancer Research UK, London Research Institute, Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Angus J M
authors.initials: AJ
authors.lastname: Cameron
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology*; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009711:Nucleotides / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009711:Nucleotides; D011494:Protein Kinases