title: New family of deamination repair enzymes in uracil-DNA glycosylase superfamily.
abstract: DNA glycosylases play a major role in the repair of deaminated DNA damage. Previous investigations identified five families within the uracil-DNA glycosylase (UDG) superfamily. All enzymes within the superfamily studied thus far exhibit uracil-DNA glycosylase activity. Here we identify a new class of DNA glycosylases in the UDG superfamily that lacks UDG activity. Instead, these enzymes act as hypoxanthine-DNA glycosylases in vitro and in vivo. Molecular modeling and structure-guided mutational analysis allowed us to identify a unique catalytic center in this class of DNA glycosylases. Based on unprecedented biochemical properties and phylogenetic analysis, we propose this new class of DNA repair glycosylases that exists in bacteria, archaea, and eukaryotes as family 6 and designate it as the hypoxanthine-DNA glycosylase family. This study demonstrates the structural evolvability that underlies substrate specificity and catalytic flexibility in the evolution of enzymatic function.
authors.affiliation: Department of Genetics and Biochemistry, South Carolina Experiment Station, Clemson University, Clemson, South Carolina 29634, USA.
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Lee
authors.forename: Brian N
authors.initials: BN
authors.lastname: Dominy
authors.forename: Weiguo
authors.initials: W
authors.lastname: Cao
mesh_terms: D002384:Catalysis; D004260:DNA Repair; D003641:Deamination; D019143:Evolution, Molecular; D006026:Glycoside Hydrolases / Q000378:metabolism*; D017021:Methanosarcina barkeri / Q000201:enzymology* / Q000235:genetics; D010802:Phylogeny; D013379:Substrate Specificity; D051981:Uracil-DNA Glycosidase / Q000378:metabolism*
chemical_list: D006026:Glycoside Hydrolases; D051981:Uracil-DNA Glycosidase; C035336:DNA-deoxyinosine glycosidase