In enzymology, a 5-formyltetrahydrofolate cyclo-ligase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are ATP and 5-formyltetrahydrofolate, whereas its 3 products are ADP, phosphate, and 5,10-methenyltetrahydrofolate.
This enzyme belongs to the family of ligases, specifically the cyclo-ligases, which form carbon-nitrogen bonds. The systematic name of this enzyme class is 5-formyltetrahydrofolate cyclo-ligase (ADP-forming). Other names in common use include 5,10-methenyltetrahydrofolate synthetase (MTHFS), formyltetrahydrofolic cyclodehydrase, and 5-formyltetrahydrofolate cyclodehydrase. This enzyme participates in one carbon pool by folate.
As of late 2007, 5 structures have been solved for this class of enzymes, with PDB accession codes , , , , and .
Mutations of the MTHFS gene cause the disease 5,10-methenyltetrahydrofolate synthetase deficiency.