Abstract
The methylenetetrahydrofolate dehydrogenase–cyclohydrolase (FolD) enzyme has a dual activity of N5,N10-methylenetetrahydrofolate dehydrogenase and cyclohydrolase. This enzyme plays a critical role in the chemical modification of tetrahydrofolate, which is an important coenzyme involved in the synthesis of DNA, RNA, and amino acids. Therefore, bacterial FolD has been studied as a potential drug target for the development of antibiotics. Here, we determined the crystal structure of FolD (PgFolD) from the oral pathogen Porphyromonas gingivalis at 2.05 Å resolution using the molecular replacement method. The crystal structure of PgFolD was successfully refined to a crystallographic R-factor of 21.4% (Rfree = 23.8%). The crystals belong to the space group of P4322 with the unit cell parameters of a = 110.7 Å, b = 110.7 Å, and c = 69.8 Å, containing one subunit in the asymmetric unit. Our analytical size-exclusion chromatography results indicated that PgFolD forms a stable dimer in solution. Additionally, structural and sequence comparison studies with previously known FolDs revealed that PgFolD has a different substrate-binding site residue composition. These findings provide valuable insights for the structure-based development of specific inhibitors against the Porphyromonas gingivalis pathogen.
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