The Catalytic Acid in the Dephosphorylation of the Cdk2-pTpY/CycA Protein Complex by Cdc25B Phosphatase

Autor(es)

Arantes, Guilherme Menegon ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Physical Chemistry B; v. 112, n. 47, p. 15244-15247, NOV 27 2008.
• Citações Web of Science: 10

Resumo

The development of anticancer therapeutics that target Cdc25 phosphatases is now an active area of research. A complete understanding of the Cdc25 catalytic mechanism would certainly allow a more rational inhibitor design. However, the identity of the catalytic acid used by Cdc25 has been debated and not established unambiguously. Results of molecular dynamics simulations with a calibrated hybrid potential for the first reaction step catalyzed by Cdc25B in complex with its natural substrate, the Cdk2-pTpY/CycA protein complex, are presented here. The calculated reaction free-energy profiles are in very good agreement with experimental measurements and are used to discern between different proposals for the general acid. In addition, the simulations give useful insight on interactions that can be explored for the design of inhibitors specific to Cdc25. (AU)

• Processo FAPESP: 07/59345-6 - Simulacao computacional em bioquimica: estrutura eletronica de agregados polinucleares em metaloenzimas e ligacao de inibidores a proteinas tirosina-fosfatases.
• Beneficiário: Guilherme Menegon Arantes
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 07/52772-6 - Simulação computacional em bioquímica: estrutura eletrônica de agregados polinucleares em metaloenzimas e ligação de inibidores a proteínas tirosina-fosfatases
• Beneficiário: Guilherme Menegon Arantes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores