View source for 8e5d


==Crystal structure of double-stranded DNA deaminase toxin DddA in complex with DNA with the target cytosine parked in the major groove==
<StructureSection load='8e5d' size='340' side='right'caption='[[8e5d]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8e5d]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_cenocepacia Burkholderia cenocepacia] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E5D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E5D 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]] 2.39&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8e5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e5d OCA], [https://pdbe.org/8e5d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e5d RCSB], [https://www.ebi.ac.uk/pdbsum/8e5d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e5d ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DDDA_BURC1 DDDA_BURC1] Toxic component of a toxin-immunity protein module, which functions as a cellular contact-dependent growth inhibition (CDI) system. CDI modules allow bacteria to communicate with and inhibit the growth of closely related neighboring bacteria in a contact-dependent fashion. Bacteria that have this module inhibit or kill bacteria without it, giving them a growth advantage. Probably specifically inhibited by cognate immunity protein DddI (Probable). The C-terminal 163 residue fragment has double-stranded DNA cytidine deaminase activity; it does not deaminate ssDNA, ssRNA or dsRNA. Leads to C:G to T:A conversions in deaminated DNA. Preferentially deaminates 5'-TC-3' substrates (PubMed:32641830).<ref>PMID:32641830</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The interbacterial deaminase toxin DddA catalyzes cytosine-to-uracil conversion in double-stranded (ds) DNA and enables CRISPR-free mitochondrial base editing, but the molecular mechanisms underlying its unique substrate selectivity have remained elusive. Here, we report crystal structures of DddA bound to a dsDNA substrate containing the 5'-TC target motif. These structures show that DddA binds to the minor groove of a sharply bent dsDNA and engages the target cytosine extruded from the double helix. DddA Phe1375 intercalates in dsDNA and displaces the 5' (-1) thymine, which in turn replaces the target (0) cytosine and forms a noncanonical T-G base pair with the juxtaposed guanine. This tandem displacement mechanism allows DddA to locate a target cytosine without flipping it into the active site. Biochemical experiments demonstrate that DNA base mismatches enhance the DddA deaminase activity and relax its sequence selectivity. On the basis of the structural information, we further identified DddA mutants that exhibit attenuated activity or altered substrate preference. Our studies may help design new tools useful in genome editing or other applications.

Structural basis of sequence-specific cytosine deamination by double-stranded DNA deaminase toxin DddA.,Yin L, Shi K, Aihara H Nat Struct Mol Biol. 2023 Aug;30(8):1153-1159. doi: 10.1038/s41594-023-01034-3. , Epub 2023 Jul 17. PMID:37460895<ref>PMID:37460895</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8e5d" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Burkholderia cenocepacia]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Aihara H]]
[[Category: Shi K]]
[[Category: Yin L]]