InterPro domain: IPR002698

5-formyltetrahydrofolate cyclo-ligase or methenyl-THF synthetase 6.3.3.2 catalyses the interchange of 5-formyltetrahydrofolate (5-FTHF) to 5-10-methenyltetrahydrofolate, this requires ATP and Mg ² [ 1 ]. 5-FTHF is used in chemotherapy where it is clinically known as Leucovorin [ 2 ].

This entry also includes the 5-formyltetrahydrofolate cyclo-ligase-like protein COG0212 (At1g76730) from Arabidopsis. It does not possess the 5-formyltetrahydrofolate cyclo-ligase activity in vitro and doesnot complement the growth defect or the characteristic 5-formyltetrahydrofolate accumulation of a 5-FCL-deficientEscherichia coli strain. Instead, it may play a role in thiamin metabolism [ 3 ].

1. Cloning and characterization of the human 5,10-methenyltetrahydrofolate synthetase-encoding cDNA. Gene 165, 307-11
2. Primary structure and tetrahydropteroylglutamate binding site of rabbit liver cytosolic 5,10-methenyltetrahydrofolate synthetase. J. Biol. Chem. 269, 18429-33
3. A 5-formyltetrahydrofolate cycloligase paralog from all domains of life: comparative genomic and experimental evidence for a cryptic role in thiamin metabolism. Funct. Integr. Genomics 11, 467-78