Uracil DNA glycosylase (UDG) activities in Bradyrhizobium diazoefficiens: characterization of a new class of UDG with broad substrate specificity. Issue 10 (28th March 2017)

• Record Type: Journal Article
• Authors: Chembazhi, Ullas Valiya; Patil, Vinod Vikas; Sah, Shivjee; Reeve, Wayne; Tiwari, Ravi P.; Woo, Euijeon; Varshney, Umesh
• Is Part Of: Nucleic acids research. Volume 45:Issue 10(2017)
• Page Start: 5863
• Page End: 5876
• Publication Date: 2017-03-28
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkx209
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Repair of uracils in DNA is initiated by u racil D NA g lycosylases (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 ( Bdi Ung) from Bradyrhizobium diazoefficiens . Although Bdi Ung contains the motif A (GQDPA), it has low sequence identity to known UDGs. Bdi Ung prefers single stranded DNA and excises uracil, 5-hydroxymethyl-uracil or xanthine from it. Bdi Ung is impervious to inhibition by AP DNA, and Ugi protein that specifically inhibits family 1 UDGs. Crystal structure of Bdi Ung 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, Bdi Ung has a uniquely extended protrusion explaining the lack of Ugi inhibition. Structural and mutational analyses of Bdi Ung have revealed the basis for the accommodation of diverse substrates into its substrate binding pocket. Phylogenetically, Bdi Ung 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.