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7omw

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Thermus sp. 2.9 DarT in complex with NAD+

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Retrieved from "http://52.214.119.220/wiki/index.php/7omw"

Categories: Large Structures | Thermus sp. 2 9 | Ariza A | Schuller M

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 == Structural highlights ==
 <table><tr><td colspan='2'>[[7omw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_sp._2.9 Thermus sp. 2.9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OMW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OMW FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">QT17_01930 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1577051 Thermus sp. 2.9])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7omw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7omw OCA], [https://pdbe.org/7omw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7omw RCSB], [https://www.ebi.ac.uk/pdbsum/7omw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7omw ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/DART_THES0 DART_THES0] Toxic component of a hybrid type II/IV toxin-antitoxin (TA) system. ADP-ribosylates ssDNA on the second thymidine of the consensus sequence 5'-TNTC-3'; the protein does not auto-modify. Arg-51 is highly flexible, allowing it to assume multiple positions in the crystal structures (PubMed:34408320). Its toxic effect is neutralized by cognate antitoxin DarG (By similarity).[UniProtKB:O53604]<ref>PMID:34408320</ref>
-ADP-ribosyltransferases use NAD(+) to catalyse substrate ADP-ribosylation(1), and thereby regulate cellular pathways or contribute to toxin-mediated pathogenicity of bacteria(2-4). Reversible ADP-ribosylation has traditionally been considered a protein-specific modification(5), but recent in vitro studies have suggested nucleic acids as targets(6-9). 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)(10). 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.
-Molecular basis for DarT ADP-ribosylation of a DNA base.,Schuller M, Butler RE, Ariza A, Tromans-Coia C, Jankevicius G, Claridge TDW, Kendall SL, Goh S, Stewart GR, Ahel I Nature. 2021 Aug;596(7873):597-602. doi: 10.1038/s41586-021-03825-4. Epub 2021, Aug 18. PMID:34408320<ref>PMID:34408320</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 7omw" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 23: / Line 16: @@
 [[Category: Large Structures]]
 [[Category: Thermus sp. 2 9]]
-[[Category: Ariza, A]]
+[[Category: Ariza A]]
-[[Category: Schuller, M]]
+[[Category: Schuller M]]
-[[Category: Adp-ribosyltransferase activity]]
-[[Category: Dna adp-ribosylation]]
-[[Category: Dna binding]]
-[[Category: Toxin]]
-[[Category: Toxin-antitoxin]]

7omw

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Thermus sp. 2.9 DarT in complex with NAD+

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