Summary for 7OMV
| Entry DOI | 10.2210/pdb7omv/pdb |
| Descriptor | DarT domain-containing protein, THIOCYANATE ION, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | toxin-antitoxin, dna adp-ribosylation, adp-ribosyltransferase activity, dna binding, toxin |
| Biological source | Thermus sp. 2.9 |
| Total number of polymer chains | 1 |
| Total formula weight | 24530.70 |
| Authors | Schuller, M.,Ariza, A. (deposition date: 2021-05-24, release date: 2021-06-23, Last modification date: 2024-05-01) |
| Primary citation | Schuller, M.,Butler, R.E.,Ariza, A.,Tromans-Coia, C.,Jankevicius, G.,Claridge, T.D.W.,Kendall, S.L.,Goh, S.,Stewart, G.R.,Ahel, I. Molecular basis for DarT ADP-ribosylation of a DNA base. Nature, 596:597-602, 2021 Cited by PubMed Abstract: ADP-ribosyltransferases use NAD to catalyse substrate ADP-ribosylation, and thereby regulate cellular pathways or contribute to toxin-mediated pathogenicity of bacteria. Reversible ADP-ribosylation has traditionally been considered a protein-specific modification, but recent in vitro studies have suggested nucleic acids as targets. Here we present evidence that specific, reversible ADP-ribosylation of DNA on thymidine bases occurs in cellulo through the DarT-DarG toxin-antitoxin system, which is found in a variety of bacteria (including global pathogens such as Mycobacterium tuberculosis, enteropathogenic Escherichia coli and Pseudomonas aeruginosa). We report the structure of DarT, which identifies this protein as a diverged member of the PARP family. We provide a set of high-resolution structures of this enzyme in ligand-free and pre- and post-reaction states, which reveals a specialized mechanism of catalysis that includes a key active-site arginine that extends the canonical ADP-ribosyltransferase toolkit. Comparison with PARP-HPF1, a well-established DNA repair protein ADP-ribosylation complex, offers insights into how the DarT class of ADP-ribosyltransferases evolved into specific DNA-modifying enzymes. Together, our structural and mechanistic data provide details of this PARP family member and contribute to a fundamental understanding of the ADP-ribosylation of nucleic acids. We also show that thymine-linked ADP-ribose DNA adducts reversed by DarG antitoxin (functioning as a noncanonical DNA repair factor) are used not only for targeted DNA damage to induce toxicity, but also as a signalling strategy for cellular processes. Using M. tuberculosis as an exemplar, we show that DarT-DarG regulates growth by ADP-ribosylation of DNA at the origin of chromosome replication. PubMed: 34408320DOI: 10.1038/s41586-021-03825-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.29 Å) |
Structure validation
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