Formimidoyltetrahydrofolate cyclodeaminase

formimidoyltetrahydrofolate cyclodeaminase
Identifiers
EC number	4.3.1.4
CAS number	9032-05-7
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

In enzymology, a formimidoyltetrahydrofolate cyclodeaminase (EC 4.3.1.4) is an enzyme that catalyzes the chemical reaction

5-formimidoyltetrahydrofolate $\rightleftharpoons$ 5,10-methenyltetrahydrofolate + NH₃

Hence, this enzyme has one substrate, 5-formimidoyltetrahydrofolate, and two products, 5,10-methenyltetrahydrofolate and NH₃.^[1]

This enzyme belongs to the family of lyases, specifically ammonia lyases, which cleave carbon-nitrogen bonds. The systematic name of this enzyme class is 5-formimidoyltetrahydrofolate ammonia-lyase (cyclizing 5,10-methenyltetrahydrofolate-forming). Other names in common use include formiminotetrahydrofolate cyclodeaminase, and 5-formimidoyltetrahydrofolate ammonia-lyase (cyclizing). This enzyme participates in folate metabolism by catabolising histidine and adding to the C₁-tetrahydrofolate pool.

In mammals, this enzyme can be found as part of a bifunctional enzyme in a single polypeptide with glutamate formimidoyltransferase (EC 2.1.2.5), the enzyme activity that catalyses the previous step in the histidine catabolic pathway.^[2] This arrangement allows the 5-formimidoyltetrahydrofolate intermediate to move directly from one active site to another without being released into solution, in a process called substrate channeling.^[3]

Structural studies

As of late 2007, 3 structures have been solved for this class of enzymes, with PDB accession codes 1O5H, 1TT9, and 2PFD.

References

1. Rabinowitz JC and Pricer WE (1956). "Formiminotetrahydrofolic acid and methenyltetrahydrofolic acid as intermediates in the formation of N10-formyltetrahydrofolic acid". J. Am. Chem. Soc. 78 (21): 5702–5704. doi:10.1021/ja01602a073.
2. MacKenzie RE, Aldridge M, Paquin J (10 October 1980). "The bifunctional enzyme formiminotransferase-cyclodeaminase is a tetramer of dimers". J. Biol. Chem. 255 (19): 9474–8. PMID 7410436.
3. Kohls D, Sulea T, Purisima EO, MacKenzie RE, Vrielink A (2000). "The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase: implications for substrate channeling in a bifunctional enzyme". Structure 8 (1): 35–46. doi:10.1016/S0969-2126(00)00078-2. PMID 10673422.