title: Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol.
abstract: Flavopiridol has been shown to potently inhibit CDK1 and 2 (cyclin-dependent kinases 1 and 2) and most recently it has been found that it also inhibits CDK9. The complex CDK9-cyclin T1 controls the elongation phase of transcription by RNA polymerase II. The present work describes a molecular model for the binary complex CDK9-flavopiridol. This structural model indicates that the inhibitor strongly binds to the ATP-binding pocket of CDK9 and the structural comparison of the complex CDK2-flavopiridol correlates the structural differences with differences in inhibition of these CDKs by flavopiridol. This structure opens the possibility of testing new inhibitor families, in addition to new substituents for the already known leading structures such as flavones and adenine derivatives.
authors.affiliation: Departamento de Física, IBILCE, UNESP, São José do Rio Preto, SP 15054-000, Brazil. walterfa@df.ibilce.unsep.br
authors.forename: Walter Filgueira
authors.initials: WF
authors.lastname: de Azevedo
authors.forename: Fernanda
authors.initials: F
authors.lastname: Canduri
authors.forename: Nelson José Freitas
authors.initials: NJ
authors.lastname: da Silveira
mesh_terms: D000595:Amino Acid Sequence; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010880:Piperidines / Q000494:pharmacology*; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases