title: Structural basis for the GSK-3beta binding affinity and selectivity against CDK-2 of 1-(4-aminofurazan-3yl)-5-dialkylaminomethyl-1H-[1,2,3] triazole-4-carboxylic acid derivatives.
abstract: A novel structural class of glycogen synthase kinase-3beta inhibitors is modeled using quantum mechanics, automated docking, and molecular dynamics simulations. The proposed binding modes identify important hydrogen bonds and salt-bridges with the ATP-binding pocket of the kinase. The modeled complexes justify the observed structure-activity relationships and provide a structural basis for the high selectivity of these inhibitors against cyclin dependent kinase-2.
authors.affiliation: REQUIMTE, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
authors.forename: Vineet
authors.initials: V
authors.lastname: Pande
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ramos
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry; D003198:Computer Simulation; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry
chemical_list: D002264:Carboxylic Acids; D047428:Protein Kinase Inhibitors; D014230:Triazoles; D000255:Adenosine Triphosphate; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051357:Cyclin-Dependent Kinase 2; D038362:Glycogen Synthase Kinase 3