Reverse Fosmidomycin Analogs as Bisubstrate Inhibitors: Binding Mode Elucidation and Mechanistic Insights

Key Points

• The study aims to elucidate the binding modes of reverse fosmidomycin analogs as inhibitors of the DXR enzyme.
• Investigated the binding interactions of introduced residues within the NADPH binding site of the DXR enzyme.
• Applied biochemical assays to determine the inhibitory capacity of fosmidomycin analogs.
• Identified that the introduced residues effectively bind to the NADPH site of the DXR enzyme.
• Demonstrated that these interactions enhance the inhibitory potential of the fosmidomycin analogs.