View source for 7lxj


==Bacillus cereus DNA glycosylase AlkD bound to a duocarmycin SA-adenine nucleobase adduct and DNA containing an abasic site==
<StructureSection load='7lxj' size='340' side='right'caption='[[7lxj]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lxj]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_cereus Bacillus cereus] 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=7LXJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LXJ 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]] 1.93&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ORP:2-DEOXY-5-PHOSPHONO-RIBOSE'>ORP</scene>, <scene name='pdbligand=YNY:methyl+(8R)-8-{[(4P)-6-amino-3H-purin-3-yl]methyl}-4-hydroxy-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-2-carboxylate'>YNY</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=7lxj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lxj OCA], [https://pdbe.org/7lxj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lxj RCSB], [https://www.ebi.ac.uk/pdbsum/7lxj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lxj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q816E8_BACCR Q816E8_BACCR] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Microbes produce a broad spectrum of antibiotic natural products, including many DNA-damaging genotoxins. Among the most potent of these are DNA alkylating agents in the spirocyclopropylcyclohexadienone (SCPCHD) family, which includes the duocarmycins, CC-1065, gilvusmycin, and yatakemycin. The yatakemycin biosynthesis cluster in Streptomyces sp. TP-A0356 contains an AlkD-related DNA glycosylase, YtkR2, that serves as a self-resistance mechanism against yatakemycin toxicity. We previously reported that AlkD, which is not present in an SCPCHD producer, provides only limited resistance against yatakemycin. We now show that YtkR2 and C10R5, a previously uncharacterized homolog found in the CC-1065 biosynthetic gene cluster of Streptomyces zelensis, confer far greater resistance against their respective SCPCHD natural products. We identify a structural basis for substrate specificity across gene clusters and show a correlation between in vivo resistance and in vitro enzymatic activity indicating that reduced product affinity-not enhanced substrate recognition-is the evolutionary outcome of selective pressure to provide self-resistance against yatakemycin and CC-1065.

Structural evolution of a DNA repair self-resistance mechanism targeting genotoxic secondary metabolites.,Mullins EA, Dorival J, Tang GL, Boger DL, Eichman BF Nat Commun. 2021 Nov 26;12(1):6942. doi: 10.1038/s41467-021-27284-7. PMID:34836957<ref>PMID:34836957</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lxj" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus cereus]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Eichman BF]]
[[Category: Mullins EA]]