title: Gas-phase studies of purine 3-methyladenine DNA glycosylase II (AlkA) substrates.
abstract: 3-Methyladenine DNA glycosylase II (AlkA) is an enzyme that cleaves a wide range of damaged bases from DNA. The gas-phase thermochemical properties (tautomerism, acidity, and proton affinity) have been measured and calculated for a series of AlkA purine substrates (7-methyladenine, 7-methylguanine, 3-methyladenine, 3-methylguanine, purine, 6-chloropurine, xanthine) that have not been heretofore examined. The damaged nucleobases are found to be more acidic than the normal nucleobases adenine and guanine. Because of this increased acidity, the damaged bases would be expected to be more easily cleaved from DNA by AlkA (their conjugate bases should be better leaving groups). We find that the gas-phase acidity correlates to the AlkA excision rates, which lends support to an AlkA mechanism wherein the enzyme provides a nonspecific active site, and nucleobase cleavage is dependent on the intrinsic N-glycosidic bond stability.
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, USA.
authors.forename: Anna Zhachkina
authors.initials: AZ
authors.lastname: Michelson
authors.forename: Mu
authors.initials: M
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Jeehiun K
authors.initials: JK
authors.lastname: Lee
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism; D020134:Catalytic Domain; D045647:DNA Glycosylases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D011522:Protons; D011687:Purines / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity; D013696:Temperature; D019820:Xanthine / Q000378:metabolism
chemical_list: D011522:Protons; D011687:Purines; D019820:Xanthine; C044502:3-methylguanine; C025946:3-methyladenine; D006147:Guanine; C008450:7-methylguanine; C059225:7-methyladenine; D045647:DNA Glycosylases; C076131:DNA-3-methyladenine glycosidase II; D000225:Adenine; C079308:6-chloropurine