Gas-phase studies of substrates for the DNA mismatch repair enzyme MutY

Anna Zhachkina Michelson, Aleksandr Rozenberg, Yuan Tian, Xuejun Sun, Julianne Davis, Anthony W. Francis, Valerie L. O'Shea, Mohan Halasyam, Amelia H. Manlove, Sheila S. David, Jeehiun K. Lee

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The gas-phase thermochemical properties (tautomeric energies, acidity, and proton affinity) have been measured and calculated for adenine and six adenine analogues that were designed to test features of the catalytic mechanism used by the adenine glycosylase MutY. The gas-phase intrinsic properties are correlated to possible excision mechanisms and MutY excision rates to gain insight into the MutY mechanism. The data support a mechanism involving protonation at N7 and hydrogen bonding to N3 of adenine. We also explored the acid-catalyzed (non-enzymatic) depurination of these substrates, which appears to follow a different mechanism than that employed by MutY, which we elucidate using calculations.

Original languageEnglish (US)
Pages (from-to)19839-19850
Number of pages12
JournalJournal of the American Chemical Society
Volume134
Issue number48
DOIs
StatePublished - Dec 5 2012

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

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    Michelson, A. Z., Rozenberg, A., Tian, Y., Sun, X., Davis, J., Francis, A. W., O'Shea, V. L., Halasyam, M., Manlove, A. H., David, S. S., & Lee, J. K. (2012). Gas-phase studies of substrates for the DNA mismatch repair enzyme MutY. Journal of the American Chemical Society, 134(48), 19839-19850. https://doi.org/10.1021/ja309082k