7N7G

Crystal Structure of FosB from Enterococcus faecium with Fosfomycin

7N7G の概要

• エントリーDOI: 10.2210/pdb7n7g/pdb
• 分子名称: Metallothiol transferase FosB, MANGANESE (II) ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: fosfomycin, antibiotic resistance, thiol-transferase, antibiotic, dimer, transferase-antibiotic complex, transferase/antibiotic
• 由来する生物種: Enterococcus faecium
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33641.24

構造登録者

Shay, M.R.,Simmons, Z.,Thompson, M.K. (登録日: 2021-06-10, 公開日: 2022-07-27, 最終更新日: 2023-10-18)

主引用文献

Wiltsie, V.,Travis, S.,Shay, M.R.,Simmons, Z.,Frantom, P.,Thompson, M.K.
Structural and functional characterization of fosfomycin resistance conferred by FosB from Enterococcus faecium.
Protein Sci., 31:580-590, 2022

PubMed Abstract: The Gram-positive pathogen Enterococcus faecium is one of the leading causes of hospital-acquired vancomycin resistant enterococci (VRE) infections. E. faecium has extensive multidrug resistance and accounts for more than two million infections in the United States each year. FosB is a fosfomycin resistance enzyme found in Gram-positive pathogens like E. faecium. Typically, the FosB enzymes are Mn -dependent bacillithiol (BSH) transferases that inactivate fosfomycin through nucleophilic addition of the thiol to the antibiotic. However, our kinetic analysis of FosB shows that the enzyme does not utilize BSH as a thiol substrate, unlike the other well characterized FosB enzymes. Here we report that FosB is a Mn -dependent L-cys transferase. In addition, we have determined the three-dimensional X-ray crystal structure of FosB in complex with fosfomycin at a resolution of 2.0 Å. A sequence similarity network (SSN) was generated for the FosB family to investigate the unexpected substrate selectivity. Three non-conserved residues were identified in the SSN that may contribute to the substrate selectivity differences in the family of enzymes. Our structural and functional characterization of FosB establishes the enzyme as a potential target and may prove useful for future structure-based development of FosB inhibitors to increase the efficacy of fosfomycin.

PubMed: 34882867
DOI: 10.1002/pro.4253

実験手法

X-RAY DIFFRACTION (2 Å)