5UUF

Bacillus cereus DNA glycosylase AlkD bound to a yatakemycin-adenine nucleobase adduct and DNA containing an abasic site (12-mer product complex)

5UUF の概要

• エントリーDOI: 10.2210/pdb5uuf/pdb
• 関連するPDBエントリー: 5UUG 5UUH 5UUJ
• 分子名称: DNA-7-methylguanine glycosylase, DNA (5'-D(*CP*CP*CP*CP*AP*(ORP)P*AP*GP*CP*CP*CP*G)-3'), DNA (5'-D(*CP*GP*GP*GP*CP*TP*TP*TP*GP*GP*GP*G)-3'), ... (5 entities in total)
• 機能のキーワード: dna glycosylase, protein-dna complex, alkylpurine, bulky lesion, hydrolase-dna-antibiotic complex, hydrolase/dna/antibiotic
• 由来する生物種: Bacillus cereus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 36603.53

構造登録者

Mullins, E.A.,Eichman, B.F. (登録日: 2017-02-16, 公開日: 2017-07-19, 最終更新日: 2023-10-04)

主引用文献

Mullins, E.A.,Shi, R.,Eichman, B.F.
Toxicity and repair of DNA adducts produced by the natural product yatakemycin.
Nat. Chem. Biol., 13:1002-1008, 2017

PubMed Abstract: 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.

PubMed: 28759018
DOI: 10.1038/nchembio.2439

実験手法

X-RAY DIFFRACTION (1.612 Å)