Uracil DNA glycosylase (UDG) activities in Bradyrhizobium diazoefficiens: characterization of a new class of UDG with broad substrate specificity
| Autor: | Vinod Vikas Patil, Wayne Reeve, Ullas V. Chembazhi, Shivjee Sah, Ravi Tiwari, Eui-Jeon Woo, Umesh Varshney |
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| Rok vydání: | 2017 |
| Předmět: |
DNA
Bacterial Models Molecular Protein Conformation alpha-Helical 0301 basic medicine Protein Folding DNA Repair DNA repair DNA Single-Stranded Gene Expression Sequence alignment Genome Integrity Repair and Replication Biology Crystallography X-Ray Substrate Specificity 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Escherichia coli Genetics Protein Interaction Domains and Motifs Amino Acid Sequence Bradyrhizobium Cloning Molecular Binding site Uracil Uracil-DNA Glycosidase Bradyrhizobium diazoefficiens Binding Sites Sequence Homology Amino Acid 030102 biochemistry & molecular biology Recombinant Proteins Kinetics 030104 developmental biology chemistry Biochemistry DNA glycosylase Uracil-DNA glycosylase Mutation Protein Conformation beta-Strand Protein Multimerization Sequence Alignment DNA DNA Damage Protein Binding |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkx209 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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