7MTT

Crystal structure of colibactin self-resistance protein ClbS in complex with two molecules of CHES

7MTT の概要

• エントリーDOI: 10.2210/pdb7mtt/pdb
• 分子名称: Colibactin self-protection protein ClbS, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID (3 entities in total)
• 機能のキーワード: hydrolase, dna repair, dna binding protein
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21162.24

構造登録者

Tripathi, P.,Bruner, S.D. (登録日: 2021-05-13, 公開日: 2021-05-26, 最終更新日: 2023-10-18)

主引用文献

Tripathi, P.,Bruner, S.D.
Structural Basis for the Interactions of the Colibactin Resistance Gene Product ClbS with DNA.
Biochemistry, 60:1619-1625, 2021

PubMed Abstract: The natural product colibactin, along with its associated biosynthetic gene cluster, is an example system for the role microbially derived small molecules play in the human microbiome. This is particularly relevant in the human gut, where host microbiota is involved in various disorders, including colorectal cancer pathogenesis. Bacteria harboring the colibactin gene cluster induce alkylation of nucleobases in host DNA, forming interstrand cross-links both and . These lesions can lead to deleterious double-strand breaks and have been identified as the primary mechanism of colibactin-induced cytotoxicity. The gene product ClbS is one of several mechanisms utilized by the producing bacteria to maintain genome integrity. ClbS catalyzes hydrolytic inactivation of colibactin and has been shown to bind DNA, incurring self-resistance. Presented is the molecular basis for ClbS bound to a DNA oligonucleotide. The structure shows the interaction of the protein with the ends of a DNA duplex with terminal nucleotides flipped to the enzyme active site. The structure suggests an additional function for ClbS, the binding to damaged DNA followed by repair. Additionally, our study provides general insight into the function of the widely distributed and largely uncharacterized DUF1706 protein family.

PubMed: 33945270
DOI: 10.1021/acs.biochem.1c00201

実験手法

X-RAY DIFFRACTION (1.85 Å)