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

Williams, Spencer J., Denehy, Emma and Krenske, Elizabeth H. (2014) 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. The Journal of Organic Chemistry, 79 5: 1995-2005. doi:10.1021/jo4026513


Author Williams, Spencer J.
Denehy, Emma
Krenske, Elizabeth H.
Title 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
Journal name The Journal of Organic Chemistry   Check publisher's open access policy
ISSN 0022-3263
1520-6904
Publication date 2014-03-01
Year available 2014
Sub-type Article (original research)
DOI 10.1021/jo4026513
Volume 79
Issue 5
Start page 1995
End page 2005
Total pages 11
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Formatted 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 SO2NH as an intermediate; theory traces this difference to the markedly greater stability of SO2NH versus SO3. For Pseudomonas aeruginosa arylsulfatase-catalyzed aryl sulfate hydrolysis, Brønsted analysis (log(Vmax/KM) versus leaving group pKa value) reveals βLG = −0.86 ± 0.23, consistent with an SN2 at sulfur reaction but substantially smaller than that reported for uncatalyzed hydrolysis (βLG = −1.81). Common to all proposed mechanisms of sulfatase catalysis is a sulfated FGly intermediate. Theory indicates a ≥26 kcal/mol preference for the intermediate to release HSO4– by an E2 mechanism, rather than alkaline phosphatase-like SN2 substitution by water. An evaluation of the stabilities of various proposed end-products of sulfamate-induced sulfatase inactivation highlights that an imine N-sulfate derived from FGly is the most likely irreversible adduct.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 04 Apr 2014, 19:39:00 EST by Elizabeth Krenske on behalf of School of Chemistry & Molecular Biosciences