title: αC helix displacement as a general approach for allosteric modulation of protein kinases.
abstract: Owing to their crucial role in the modulation of cell pathways, protein kinases are important targets for several human diseases, including but not limited to cancer. The classic approach of targeting the ATP active site has recently come up against selectivity issues, which can be considerably reduced by following an allosteric modulation approach. Being closely related to protein kinase inactivation, allosteric targeting via displacement of the conserved structural αC helix enables a direct and specific modulation mechanism. A structure-based survey of the allosteric regulation of αC helix conformation in various kinase families is provided, highlighting key allosteric pockets and modulation mechanisms that appear to be more broadly conserved than was previously thought.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, 41125 Modena, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Palmieri
authors.forename: Giulio
authors.initials: G
authors.lastname: Rastelli
mesh_terms: D000494:Allosteric Regulation; D001665:Binding Sites; D055808:Drug Discovery; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary
chemical_list: D047428:Protein Kinase Inhibitors; D011494:Protein Kinases