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The Catalytic Mechanism of Protein Phosphatase 5 Established by DFT Calculations
Author(s) -
Ribeiro António J. M.,
Alberto Marta E.,
Ramos Maria J.,
Fernandes Pedro A.,
Russo Nino
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201301565
Subject(s) - protonation , serine , catalysis , threonine , cluster (spacecraft) , chemistry , density functional theory , transition state , mechanism (biology) , computational chemistry , phosphatase , ion , active site , active center , stereochemistry , phosphorylation , physics , biochemistry , organic chemistry , quantum mechanics , computer science , programming language
In order to elucidate the catalytic mechanism of the Mn–Mn containing serine/threonine protein phosphatase 5 (PP5), we present a density functional theory study with a cluster model approach. According to our results, the reaction occurs through an in‐line concerted transition state with an energy of 15.8 kcal mol −1 , and no intermediates are formed. The important role played by His304 and Asp274 as stabilizers of the leaving group has been shown, whereas the role played by the metal ions seems to be mostly electrostatic. The indispensable requirement of having a neutral active center has been demonstrated by testing different protonation states of the cluster model. We have shown also the importance of describing properly the electronic configuration of the Mn–Mn binuclear centers.