7lxj

Bacillus cereus DNA glycosylase AlkD bound to a duocarmycin SA-adenine nucleobase adduct and DNA containing an abasic site

spinqualitylabelsall models 7lxj, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7lxj is a 3 chain structure with sequence from Bacillus cereus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.93Å Ligands: CA, ORP, YNY Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q816E8_BACCR 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA glycosylase 3D structures

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