7n7g

Crystal Structure of FosB from Enterococcus faecium with Fosfomycin

spinqualitylabelsall models 7n7g, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7n7g is a 2 chain structure with sequence from Enterococcus faecium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: EDO, FCN, MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F1C939_ENTFC Publication Abstract from PubMed 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(2+) -dependent bacillithiol (BSH) transferases that inactivate fosfomycin through nucleophilic addition of the thiol to the antibiotic. However, our kinetic analysis of FosB(Ef) shows that the enzyme does not utilize BSH as a thiol substrate, unlike the other well characterized FosB enzymes. Here we report that FosB(Ef) is a Mn(2+) -dependent L-cys transferase. In addition, we have determined the three-dimensional X-ray crystal structure of FosB(Ef) in complex with fosfomycin at a resolution of 2.0 A. 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(Ef) 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. Structural and functional characterization of fosfomycin resistance conferred by FosB from Enterococcus faecium.,Wiltsie V, Travis S, Shay MR, Simmons Z, Frantom P, Thompson MK Protein Sci. 2022 Mar;31(3):580-590. doi: 10.1002/pro.4253. Epub 2021 Dec 22. PMID:34882867 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Metallothiol transferase FosB

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