Conformational flexibility of the complete catalytic domain of Cdc25B phosphatases.

Autor: Sayegh RS; Departamento De Bioquímica, Instituto De Química, Universidade De São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, Brazil., Tamaki FK; Departamento De Bioquímica, Instituto De Química, Universidade De São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, Brazil., Marana SR; Departamento De Bioquímica, Instituto De Química, Universidade De São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, Brazil., Salinas RK; Departamento De Bioquímica, Instituto De Química, Universidade De São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, Brazil., Arantes GM; Departamento De Bioquímica, Instituto De Química, Universidade De São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, Brazil. garantes@iq.usp.br.
Jazyk: angličtina
Zdroj: Proteins [Proteins] 2016 Nov; Vol. 84 (11), pp. 1567-1575. Date of Electronic Publication: 2016 Jul 25.
DOI: 10.1002/prot.25100
Abstrakt: Cdc25B phosphatases are involved in cell cycle checkpoints and have become a possible target for developing new anticancer drugs. A more rational design of Cdc25B ligands would benefit from detailed knowledge of its tertiary structure. The conformational flexibility of the C-terminal region of the Cdc25B catalytic domain has been debated recently and suggested to play an important structural role. Here, a combination of experimental NMR measurements and molecular dynamics simulations for the complete catalytic domain of the Cdc25B phosphatase is presented. The stability of the C-terminal α-helix is confirmed, but the last 20 residues in the complete catalytic domain are very flexible, partially occlude the active site and may establish transient contacts with the protein core. This flexibility in the C-terminal tail may modulate the molecular recognition of natural substrates and competitive inhibitors by Cdc25B. Proteins 2016; 84:1567-1575. © 2016 Wiley Periodicals, Inc.
(© 2016 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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