title: 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.
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, United States.
authors.forename: Anna Zhachkina
authors.initials: AZ
authors.lastname: Michelson
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Rozenberg
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.forename: Xuejun
authors.initials: X
authors.lastname: Sun
authors.forename: Julianne
authors.initials: J
authors.lastname: Davis
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Francis
authors.forename: Valerie L
authors.initials: VL
authors.lastname: O'Shea
authors.forename: Mohan
authors.initials: M
authors.lastname: Halasyam
authors.forename: Amelia H
authors.initials: AH
authors.lastname: Manlove
authors.forename: Sheila S
authors.initials: SS
authors.lastname: David
authors.forename: Jeehiun K
authors.initials: JK
authors.lastname: Lee
mesh_terms: D000225:Adenine / Q000737:chemistry; D002384:Catalysis; D045647:DNA Glycosylases / Q000737:chemistry*; D053843:DNA Mismatch Repair; D005740:Gases / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D044367:Phase Transition; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D005740:Gases; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; D000225:Adenine