Serine hydroxymethyltransferase (SHMT) plays a critical role in the 1C metabolism pathway. This pathway is involved in the synthesis of many amino and nucleic acids, and SHMT is considered a target for drugs through folate metabolism, especially for cancer and malaria. A detailed analysis of the interactions between SHMTs and drugs will greatly contribute to the development of new drugs. An anthraquinone compound was found in a compound library screening against SHMT from Enterococcus faecium (efmSHMT), from which mangiferin was implied as a compound that binds to efmSHMT. The binding assay indicated that mangiferin could bind to efmSHMT, and crystal structure analysis revealed interactions between efmSHMT and mangiferin at the binding site. Mangiferin bound to the binding site, turning the glucose moiety inward, which was supported by the docking model study. Although mangiferin does not share its molecular structure with other known inhibitors, such as pyrazolopyran-based compounds, the complex structure of the binding site did not differ much from those of other structures. The ligand binding site of efmSHMT may possess a preferred conformation.
Keywords: 1C-metabolism; Complex structure; Inhibitor; Xanthone glycoside.
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