8B7S

Crystal structure of the Chloramphenicol-inactivating oxidoreductase from Novosphingobium sp

8B7S の概要

• エントリーDOI: 10.2210/pdb8b7s/pdb
• 分子名称: Chloramphenicol-inactivating oxidoreductase, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: cap-ohase, chloramphenicol, oxidoreductase, flavin, fad, cap, anitmicrobial resistance, flavoprotein
• 由来する生物種: Novosphingobium sp. B 225
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 59505.05

構造登録者

Zhang, L.,Toplak, M.,Saleem-Batcha, R.,Hoeing, L.,Jakob, R.P.,Jehmlich, N.,von Bergen, M.,Maier, T.,Teufel, R. (登録日: 2022-10-03, 公開日: 2022-11-16, 最終更新日: 2024-05-01)

主引用文献

Zhang, L.,Toplak, M.,Saleem-Batcha, R.,Hoing, L.,Jakob, R.,Jehmlich, N.,von Bergen, M.,Maier, T.,Teufel, R.
Bacterial Dehydrogenases Facilitate Oxidative Inactivation and Bioremediation of Chloramphenicol.
Chembiochem, 24:e202200632-e202200632, 2023

PubMed Abstract: Antimicrobial resistance represents a major threat to human health and knowledge of the underlying mechanisms is therefore vital. Here, we report the discovery and characterization of oxidoreductases that inactivate the broad-spectrum antibiotic chloramphenicol via dual oxidation of the C3-hydroxyl group. Accordingly, chloramphenicol oxidation either depends on standalone glucose-methanol-choline (GMC)-type flavoenzymes, or on additional aldehyde dehydrogenases that boost overall turnover. These enzymes also enable the inactivation of the chloramphenicol analogues thiamphenicol and azidamfenicol, but not of the C3-fluorinated florfenicol. Notably, distinct isofunctional enzymes can be found in Gram-positive (e. g., Streptomyces sp.) and Gram-negative (e. g., Sphingobium sp.) bacteria, which presumably evolved their selectivity for chloramphenicol independently based on phylogenetic analyses. Mechanistic and structural studies provide further insights into the catalytic mechanisms of these biotechnologically interesting enzymes, which, in sum, are both a curse and a blessing by contributing to the spread of antibiotic resistance as well as to the bioremediation of chloramphenicol.

PubMed: 36353978
DOI: 10.1002/cbic.202200632

実験手法

X-RAY DIFFRACTION (2.1 Å)