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

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.

SUBMITTER: Michelson AZ

PROVIDER: S-EPMC4204490 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

Michelson Anna Zhachkina AZ Rozenberg Aleksandr A Tian Yuan Y Sun Xuejun X Davis Julianne J Francis Anthony W AW O'Shea Valerie L VL Halasyam Mohan M Manlove Amelia H AH David Sheila S SS Lee Jeehiun K JK

Journal of the American Chemical Society 20121126 48

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 a ...[more]

PMID: 23106240

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