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Conformational flexibility of the complete catalytic domain of Cdc25B phosphatases
Author(s) -
Sayegh Raphael S. R.,
Tamaki Fabio K.,
Marana Sandro R.,
Salinas Roberto K.,
Arantes Guilherme M.
Publication year - 2016
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25100
Subject(s) - chemistry , rational design , molecular dynamics , flexibility (engineering) , catalytic cycle , phosphatase , protein structure , active site , catalysis , biophysics , computational biology , stereochemistry , enzyme , biochemistry , nanotechnology , biology , materials science , computational chemistry , statistics , mathematics
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.