5uuh | pdb_00005uuh

Bacillus cereus DNA glycosylase AlkD bound to a yatakemycin-adenine nucleobase adduct and DNA containing a fluorinated abasic site (9-mer product complex)

spinqualitylabelsall models 5uuh, resolution 1.57Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5uuh is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, YTA, RF5 Related: 5uuf, 5uug, 5uuj Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Yatakemycin (YTM) is an extraordinarily toxic DNA alkylating agent with potent antimicrobial and antitumor properties and is the most recent addition to the CC-1065 and duocarmycin family of natural products. Though bulky DNA lesions the size of those produced by YTM are normally removed from the genome by the nucleotide-excision repair (NER) pathway, YTM adducts are also a substrate for the bacterial DNA glycosylases AlkD and YtkR2, unexpectedly implicating base-excision repair (BER) in their elimination. The reason for the extreme toxicity of these lesions and the molecular basis for the way they are eliminated by BER have been unclear. Here, we describe the structural and biochemical properties of YTM adducts that are responsible for their toxicity, and define the mechanism by which they are excised by AlkD. These findings delineate an alternative strategy for repair of bulky DNA damage and establish the cellular utility of this pathway relative to that of NER. Toxicity and repair of DNA adducts produced by the natural product yatakemycin.,Mullins EA, Shi R, Eichman BF Nat Chem Biol. 2017 Jul 24. doi: 10.1038/nchembio.2439. PMID:28759018 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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