Journal article
Experimental and theoretical insights into the mechanisms of sulfate and sulfamate ester hydrolysis and the end products of type i sulfatase inactivation by aryl sulfamates
SJ Williams, E Denehy, EH Krenske
Journal of Organic Chemistry | Published : 2014
DOI: 10.1021/jo4026513
Abstract
Type I sulfatases catalyze the hydrolysis of sulfate esters through S-O bond cleavage and possess a catalytically essential formylglycine (FGly) active-site residue that is post-translationally derived from either cysteine or serine. Type I sulfatases are inactivated by aryl sulfamates in a time-dependent, irreversible, and active-site directed manner consistent with covalent modification of the active site. We report a theoretical (SCS-MP2//B3LYP) and experimental study of the uncatalyzed and enzyme-catalyzed hydrolysis of aryl sulfates and sulfamates. In solution, aryl sulfate monoanions undergo hydrolysis by an SN2 mechanism whereas aryl sulfamate monoanions follow an SN1 pathway with SO2..
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Funding Acknowledgements
We thank the Australian Research Council and the ARC Centre of Excellence for Free Radical Chemistry and Biotechnology and the Selby Foundation for financial support. High-performance computer resources were provided by the National Computational Infrastructure National Facility (Australia), the University of Queensland Research Computing Centre, and the University of Melbourne. E.D. was supported by a Sir John and Lady Higgins Scholarship. S.J.W. and E.H.K. are Future Fellows funded by the Australian Research Council.