7ZHE

Crystal structure of CtaZ from Ruminiclostridium cellulolyticum

7ZHE の概要

• エントリーDOI: 10.2210/pdb7zhe/pdb
• 関連するPDBエントリー: 6WL5 7ZHD
• 分子名称: Transcription activator effector binding, GLYCEROL, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: gyrase-like domain, receptor, siderophore, self protection, antibiotic resistance, drug binding, lipid binding protein
• 由来する生物種: Ruminiclostridium cellulolyticum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17688.48

構造登録者

Gude, F.,Molloy, E.M.,Horch, T.,Dell, M.,Dunbar, K.L.,Krabbe, J.,Groll, M.,Hertweck, C. (登録日: 2022-04-06, 公開日: 2022-11-09, 最終更新日: 2024-01-31)

主引用文献

Gude, F.,Molloy, E.M.,Horch, T.,Dell, M.,Dunbar, K.L.,Krabbe, J.,Groll, M.,Hertweck, C.
A Specialized Polythioamide-Binding Protein Confers Antibiotic Self-Resistance in Anaerobic Bacteria.
Angew.Chem.Int.Ed.Engl., 61:e202206168-e202206168, 2022

PubMed Abstract: Understanding antibiotic resistance mechanisms is central to the development of anti-infective therapies and genomics-based drug discovery. Yet, many knowledge gaps remain regarding the resistance strategies employed against novel types of antibiotics from less-explored producers such as anaerobic bacteria, among them the Clostridia. Through the use of genome editing and functional assays, we found that CtaZ confers self-resistance against the copper chelator and gyrase inhibitor closthioamide (CTA) in Ruminiclostridium cellulolyticum. Bioinformatics, biochemical analyses, and X-ray crystallography revealed CtaZ as a founding member of a new group of GyrI-like proteins. CtaZ is unique in binding a polythioamide scaffold in a ligand-optimized hydrophobic pocket, thereby confining CTA. By genome mining using CtaZ as a handle, we discovered previously overlooked homologs encoded by diverse members of the phylum Firmicutes, including many pathogens. In addition to characterizing both a new role for a GyrI-like domain in self-resistance and unprecedented thioamide binding, this work aids in uncovering related drug-resistance mechanisms.

PubMed: 35852818
DOI: 10.1002/anie.202206168

実験手法

X-RAY DIFFRACTION (2 Å)