Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 286, Issue 36, Pages 31282-31287Publisher
ELSEVIER
DOI: 10.1074/jbc.M111.249524
Keywords
-
Categories
Funding
- National Institutes of Health [GM090141]
- Cooperative State Research, Education, and Extension Service/United States Department of Agriculture [SC-1700274, 5905]
- United States Department of Defense [W81XWH-10-1-0385]
- National Science Foundation [MCB-0953783]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [0953783] Funding Source: National Science Foundation
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available