Formimidoyltetrahydrofolate cyclodeaminase

formimidoyltetrahydrofolate cyclodeaminase
Identifiers
EC no.	4.3.1.4
CAS no.	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 / QuickGO
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 ${\displaystyle \rightleftharpoons }$ 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; 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. Bibcode:1956JAChS..78.5702R. 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. doi: 10.1016/S0021-9258(19)70586-9 . 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.