Chembazhi, Ullas Valiya and Patil, Vinod Vikas and Sah, Shivjee and Reeve, Wayne and Tiwari, Ravi P. and Woo, Euijeon and Varshney, Umesh (2017) Uracil DNA glycosylase (UDG) activities in Bradyrhizobium diazoefficiens: characterization of a new class of UDG with broad substrate specificity. In: Nucleic Acids Research, 45 (10). pp. 5863-5876. ISSN 0305-1048
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Abstract
Repair of uracils in DNA is initiated by uracil DNA glycosylases (UDGs). Family 1 UDGs (Ung) are the most efficient and ubiquitous proteins having an exquisite specificity for uracils in DNA. Ung are characterized by motifs A (GQDPY) and B (HPSPLS) sequences. We report a novel dimeric UDG, Blr0248 (BdiUng) from Bradyrhizobium diazoefficiens. Although BdiUng contains the motif A (GQDPA), it has low sequence identity to known UDGs. BdiUng prefers single stranded DNA and excises uracil, 5-hydroxymethyl-uracil or xanthine from it. BdiUng is impervious to inhibition by AP DNA, and Ugi protein that specifically inhibits family 1 UDGs. Crystal structure of BdiUng shows similarity with the family 4 UDGs in its overall fold but with family 1 UDGs in key active site residues. However, instead of a classical motif B, BdiUng has a uniquely extended protrusion explaining the lack of Ugi inhibition. Structural and mutational analyses of BdiUng have revealed the basis for the accommodation of diverse substrates into its substrate binding pocket. Phylogenetically, BdiUng belongs to a new UDG family. Bradyrhizobium diazoefficiens presents a unique scenario where the presence of at least four families of UDGs may compensate for the absence of an efficient family 1 homologue.
| Item Type: | Journal Article |
|---|---|
| Publication: | Nucleic Acids Research |
| Publisher: | Oxford University Press |
| Additional Information: | The copyright of this article belongs to the author. |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 02 Jun 2022 06:34 |
| Last Modified: | 02 Jun 2022 06:34 |
| URI: | https://eprints.iisc.ac.in/id/eprint/73063 |
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