Molecular models of cyclin-dependent kinase 1 complexed with inhibitors

Autor(es)

Canduri, Fernanda ; Uchôa, Hugo Brandão ; Azevedo Júnior, Walter Filgueira de ^[3]

• Tipo de documento: Artigo Científico
• Fonte: Biochemical and Biophysical Research Communications; v. 324, n. 2, p. 661-666, Nov. 2004.
• Assunto(s): Biofísica Biologia computacional

Resumo

Roscovitine and flavopiridol have been shown to potently inhibit cyclin-dependent kinase 1 and 2 (CDK1 and 2). The structures of CDK2 complexed with roscovitine and deschoroflavopiridol have been reported, however no crystallographic structure is available for complexes of CDK1 with inhibitors. The present work describes two molecular models for the binary complexes CDK1:roscovitine and CDK1:flavopiridol. These structural models indicate that both inhibitors strongly bind to the ATP-binding pocket of CDK1 and structural comparison of the CDK complexes correlates the structures with differences in inhibition of these CDKs by flavopiridol and roscovitine. This article explains the structural basis for the observed differences in activity of these inhibitors. (AU)

• Processo FAPESP: 01/07532-0 - Structural genomics of cyclin dependent kinases and plant defensive proteinases and their natural inhibitors
• Beneficiário: Walter Filgueira de Azevedo Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/00217-0 - Estudo estrutural de proteinas alvos para desenho de drogas contra tuberculose.
• Beneficiário: Walter Filgueira de Azevedo Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 02/04383-7 - Estudo estrutural das enzimas da via metabólica do ácido chiquímico
• Beneficiário: Walter Filgueira de Azevedo Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular