5m3i
From Proteopedia
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(New page: '''Unreleased structure''' The entry 5m3i is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Macrodomain of Mycobacterium tuberculosis DarG== | |
| + | <StructureSection load='5m3i' size='340' side='right'caption='[[5m3i]], [[Resolution|resolution]] 2.17Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5m3i]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M3I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M3I FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.17Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=5m3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m3i OCA], [https://pdbe.org/5m3i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m3i RCSB], [https://www.ebi.ac.uk/pdbsum/5m3i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m3i ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DARG_MYCTU DARG_MYCTU] Antitoxin component of a hybrid type II/IV toxin-antitoxin (TA) system. De-ADP-ribosylates DNA (probably) modified on thymidine by its cognate toxin DarT, which neutralizes the activity of DarT (PubMed:27939941). Experiments in which DarG levels are depleted lead to cell death; expression of wild-type DarG protein from M.tuberculosis or T.aquaticus restores growth. Cells depleted of DarG are more sensitive to bedaquilline (targets respiration), DNA-damaging drugs (mitomycin C, netropsin) and transcription-targeted drugs (rifabutin and rifampicin). When depleted, a DNA-damage response is induced and mutability is increased (PubMed:32634279). In E.coli the macrodomain alone neutralizes DarT toxin from non-cognate T.aquaticus. The same domain de-ADP-ribosylates genomic DNA (PubMed:34408320).<ref>PMID:27939941</ref> <ref>PMID:32634279</ref> <ref>PMID:34408320</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The discovery and study of toxin-antitoxin (TA) systems helps us advance our understanding of the strategies prokaryotes employ to regulate cellular processes related to the general stress response, such as defense against phages, growth control, biofilm formation, persistence, and programmed cell death. Here we identify and characterize a TA system found in various bacteria, including the global pathogen Mycobacterium tuberculosis. The toxin of the system (DarT) is a domain of unknown function (DUF) 4433, and the antitoxin (DarG) a macrodomain protein. We demonstrate that DarT is an enzyme that specifically modifies thymidines on single-stranded DNA in a sequence-specific manner by a nucleotide-type modification called ADP-ribosylation. We also show that this modification can be removed by DarG. Our results provide an example of reversible DNA ADP-ribosylation, and we anticipate potential therapeutic benefits by targeting this enzyme-enzyme TA system in bacterial pathogens such as M. tuberculosis. | ||
| - | + | The Toxin-Antitoxin System DarTG Catalyzes Reversible ADP-Ribosylation of DNA.,Jankevicius G, Ariza A, Ahel M, Ahel I Mol Cell. 2016 Dec 15;64(6):1109-1116. doi: 10.1016/j.molcel.2016.11.014. Epub, 2016 Dec 8. PMID:27939941<ref>PMID:27939941</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5m3i" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium tuberculosis]] | ||
| + | [[Category: Ariza A]] | ||
Current revision
Macrodomain of Mycobacterium tuberculosis DarG
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