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Sulfonium Ion Condensation: The Burden Borne by SAM Synthetase.

Authors
  • Lewis, Charles A Jr1
  • Wolfenden, Richard1
  • 1 From the Department of Biochemistry and Biophysics , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599-7260 , United States. , (United States)
Type
Published Article
Journal
Biochemistry
Publisher
American Chemical Society
Publication Date
May 31, 2018
Identifiers
DOI: 10.1021/acs.biochem.8b00477
PMID: 29787240
Source
Medline
License
Unknown

Abstract

S-Adenosylmethionine (SAM+) serves as the principal methylating agent in biological systems, but the thermodynamic basis of its reactivity does not seem to have been clearly established. Here, we show that methionine, methanol, and H+ combine to form S-methylmethionine (SMM+) with a temperature-independent equilibrium constant of 9.9 M-2. The corresponding group transfer potential of SMM+ (its free energy of hydrolysis at pH 7) is -8.2 kcal/mol. The "energy-rich" nature of sulfonium ions is related to the extreme acidity (p Ka -5.4) of the S-protonated thioether produced by sulfonium hydrolysis, and the large negative free energy of deprotonation of that species in neutral solution (-16.7 kcal/mol). At pH 7, SAM synthetase requires the free energy released by cleavage of two bonds of ATP to reverse that process.

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