title: Molecular model of cyclin-dependent kinase 5 complexed with roscovitine.
abstract: Here is described a structural model for the binary complex CDK5-roscovitine. Roscovitine has been shown to potently inhibit cyclin-dependent kinases 1, 2 and 5 (CDK1, 2, and 5), and the structure of CDK2 complexed with roscovitine has been reported; however, no structural data are available for complexes of CDK5 with inhibitors. The structural model indicates that roscovitine strongly binds to the ATP-binding pocket of CDK5 and structural comparison of the CDK2-roscovitine complex correlates the structural differences with differences in inhibition of these CDKs by this inhibitor. This structure opens the possibility of testing new inhibitor families, in addition to new substituents for the already known lead structures of adenine derivatives.
authors.affiliation: Departamento de Fi;sica, IBILCE, UNESP 15054-000, São José do Rio Preto, SP, Brazil. walterfa@df.ibile.unesp.br
authors.forename: Walter
authors.initials: W
authors.lastname: Filgueira de Azevedo
authors.forename: Renato Tadeu
authors.initials: RT
authors.lastname: Gaspar
authors.forename: Fernanda
authors.initials: F
authors.lastname: Canduri
authors.forename: João Carlos
authors.initials: JC
authors.lastname: Camera
authors.forename: Nelson José
authors.initials: NJ
authors.lastname: Freitas da Silveira
mesh_terms: D000225:Adenine / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011687:Purines / Q000737:chemistry*; D000077546:Roscovitine; D017386:Sequence Homology, Amino Acid; D012984:Software
chemical_list: D004791:Enzyme Inhibitors; D011687:Purines; D000077546:Roscovitine; D000255:Adenosine Triphosphate; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495905:CDK5 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D000225:Adenine