title: Gas-Phase Studies of Formamidopyrimidine Glycosylase (Fpg) Substrates.
abstract: Gas-phase thermochemical properties (tautomerism, acidity, and proton affinity) have been measured and calculated for a series of nucleobase derivatives that have not heretofore been examined under vacuum. The studied species are substrates for the enzyme formamidopyrimidine glycosylase (Fpg), which cleaves damaged nucleobases from DNA. The gas-phase results are compared and contrasted to solution-phase data, to afford insight into the Fpg mechanism. Calculations are also used to probe the energetics of various possible mechanisms and to predict isotope effects that could potentially allow for discrimination between different mechanisms. Specifically, (18) O substitution at the ribose O4' is predicted to result in a normal kinetic isotope effect (KIE) for a ring-opening "endocyclic" mechanism and an inverse KIE for a direct base excision "exocyclic" pathway.
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA.
authors.forename: G S M
authors.initials: GS
authors.lastname: Kiruba
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Zelikson
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA. jee.lee@rutgers.edu.
authors.forename: Jeehiun K
authors.identifier: http://orcid.org/0000-0002-1665-1604
authors.initials: JK
authors.lastname: Lee
mesh_terms: D020029:Base Pairing; D045647:DNA Glycosylases / Q000737:chemistry* / Q000378:metabolism; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase / Q000737:chemistry* / Q000378:metabolism; D005740:Gases / Q000737:chemistry*; D007700:Kinetics; D012996:Solutions; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D005740:Gases; D012996:Solutions; D045647:DNA Glycosylases; D043382:DNA-Formamidopyrimidine Glycosylase
keywords: ab initio calculations; gas phase studies; ion-molecule reactions; nucleosides; physical organic chemistry