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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Arantes, Guilherme Menegon [1]
Total Authors: 1
Affiliation:
[1] Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508900 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Journal of Physical Chemistry B; v. 112, n. 47, p. 15244-15247, NOV 27 2008.
Web of Science Citations: 10
Abstract

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)