Gas-Phase Studies of Substrates for the DNA Mismatch Repair Enzyme MutY
journal contributionposted on 05.12.2012 by 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
Any type of content formally published in an academic journal, usually following a peer-review process.
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.