title: Conformational flexibility of the complete catalytic domain of Cdc25B phosphatases.
abstract: 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.
authors.affiliation: Departamento De Bioquímica, Instituto De Química, Universidade De São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, Brazil.
authors.forename: Raphael S R
authors.initials: RS
authors.lastname: Sayegh
authors.affiliation: Departamento De Bioquímica, Instituto De Química, Universidade De São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, Brazil.
authors.forename: Fabio K
authors.initials: FK
authors.lastname: Tamaki
authors.affiliation: Departamento De Bioquímica, Instituto De Química, Universidade De São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, Brazil.
authors.forename: Sandro R
authors.initials: SR
authors.lastname: Marana
authors.affiliation: Departamento De Bioquímica, Instituto De Química, Universidade De São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, Brazil.
authors.forename: Roberto K
authors.initials: RK
authors.lastname: Salinas
authors.affiliation: Departamento De Bioquímica, Instituto De Química, Universidade De São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, Brazil. garantes@iq.usp.br.
authors.forename: Guilherme M
authors.identifier: 0000-0001-5356-7703
authors.initials: GM
authors.lastname: Arantes
mesh_terms: D020816:Amino Acid Motifs; D020134:Catalytic Domain; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D018583:Pliability; D055550:Protein Stability; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases
keywords: NMR spectroscopy; computer simulation; molecular dynamics; protein dynamics; protein phosphatase