Taxonomic distribution of proteins containing FTCD domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing FTCD domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

The crystal structure of the formiminotransferase domain offormiminotransferase-cyclodeaminase: implications for substrate channeling in abifunctional enzyme.

Kohls D, Sulea T, Purisima EO, MacKenzie RE, Vrielink A
Structure. 2000; 8: 35-46

BACKGROUND: The bifunctional enzyme formiminotransferase-cyclodeaminase (FTCD)contains two active sites at different positions on the protein structure. Theenzyme binds a gamma-linked polyglutamylated form of the tetrahydrofolatesubstrate and channels the product of the transferase reaction from thetransferase active site to the cyclodeaminase active site. Structural studies of this bifunctional enzyme and its monofunctional domains will provide insight intothe mechanism of substrate channeling and the two catalytic reactions. RESULTS:The crystal structure of the formiminotransferase (FT) domain of FTCD has beendetermined in the presence of a product analog, folinic acid. The overallstructure shows that the FT domain comprises two subdomains that adopt a novelalpha/beta fold. Inspection of the folinic acid binding site reveals anelectrostatic tunnel traversing the width of the molecule. The distribution ofcharged residues in the tunnel provides insight into the possible mode ofsubstrate binding and channeling. The electron density reveals that thenon-natural stereoisomer, (6R)-folinic acid, binds to the protein; thisobservation suggests a mechanism for product release. In addition, a singlemolecule of glycerol is bound to the enzyme and indicates a putative binding sitefor formiminoglutamate. CONCLUSIONS: The structure of the FT domain in thepresence of folinic acid reveals a possible novel mechanism for substratechanneling. The position of the folinic acid and a bound glycerol molecule nearto the sidechain of His82 suggests that this residue may act as the catalyticbase required for the formiminotransferase mechanism.