Cyclodeaminase domain

In molecular biology, enzymes containing the cyclodeaminase domain function in channeling one-carbon units to the folate pool. In most cases, this domain acts as a formimidoyltetrahydrofolate cyclodeaminase, which catalyses the cyclisation of formimidoyltetrahydrofolate to methenyltetrahydrofolate as shown in reaction (1). In the methylotrophic bacterium Methylobacterium extorquens, however, it acts as a methenyltetrahydrofolate cyclohydrolase, which catalyses the interconversion of formyltetrahydrofolate and methylenetetrahydrofolate, as shown in reaction (2).^[1]

FTCD_C
crystal structure of formiminotetrahydrofolate cyclodeaminase (tm1560) from thermotoga maritima at 2.80 a resolution
Identifiers
Symbol	FTCD_C
Pfam	PF04961
InterPro	IPR007044
SCOP2	1o5h / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

(1) 5-formimidoyltetrahydrofolate = 5,10-methenyltetrahydrofolate + NH(3)

(2) 10- formyltetrahydrofolate = 5,10-methenyltetrahydrofolate + H(2)O

In prokaryotes, this domain mostly occurs on its own, while in eukaryotes it is fused to a glutamate formiminotransferase domain (which catalyses the previous step in the pathway) to form the bifunctional enzyme formiminotransferase cyclodeaminase.^[2] The eukaryotic enzyme is a circular tetramer of homodimers, while the prokaryotic enzyme is a dimer.^[1][3][4]

The crystal structure of the cyclodeaminase enzyme from Thermaotogoa maritima has been studied.^[4] It is a homodimer, where each monomer is composed of six alpha helices arranged in an up and down helical bundle, forming a novel fold. The location of the active site is not known, but sequence alignments revealed two clusters of conserved residues located in a deep pocket within the dimmer interface. This pocket was large enough to accommodate the reaction product and it was postulated that this is the active site.