Glutamate formimidoyltransferase

 

Tetrahydrofolate (THF)-dependent glutamate formiminotransferase is involved in the histidine utilisation pathway.

 

Reference Protein and Structure

Sequence
P53603 UniProt (2.1.2.5, 4.3.1.4) IPR004227 (Sequence Homologues) (PDB Homologues)
Biological species
Sus scrofa (pig) Uniprot
PDB
1qd1 - THE CRYSTAL STRUCTURE OF THE FORMIMINOTRANSFERASE DOMAIN OF FORMIMINOTRANSFERASE-CYCLODEAMINASE. (1.7 Å) PDBe PDBsum 1qd1
Catalytic CATH Domains
3.30.990.10 CATHdb (see all for 1qd1)
Click To Show Structure

Enzyme Reaction (EC:2.1.2.5)

5-formimidoyltetrahydrofolate(2-)
CHEBI:57456ChEBI
+
L-glutamate(1-)
CHEBI:29985ChEBI
→
(6S)-5,6,7,8-tetrahydrofolate(2-)
CHEBI:57453ChEBI
+
N-formimidoyl-L-glutamate(1-)
CHEBI:58928ChEBI
Alternative enzyme names: Formiminoglutamic acid transferase, Formiminoglutamic formiminotransferase, Glutamate formiminotransferase, Glutamate formyltransferase,

Enzyme Mechanism

Introduction

The reaction catalyzed by the N-terminal domian of FTCD transfers the formimino group from formiminoglutamate to tetrahydrofolate and subsequently carries out a cyclodeamination to give N5,N10-methenyltetrahydrofolate. The precise mechanism for the reactions and the residues important for catalysis and substrate binding are not yet known. However, the N5 atom of the substrate, the nucleophile expected to attack the imino carbon of formiminoglutamate, is completely buried from the external surface of the protein. Such a buried environment will protect the labile N5-formiminotetrahydrofolate product of the formiminotransferase reaction from hydrolysis.

Catalytic Residues Roles

UniProt PDB* (1qd1)
His82 His82(81)A The presence of a histidine (His82) near the substrate suggests that this residue acts as a general acid/base, abstracting the proton from N5 of tetrahydrofolate, thus increasing its nucleophilicity for attack at the imino carbon atom of formiminoglutamate. The protonated His82 could subsequently facilitate the breakdown of the intermediate by protonating the amino group of the glutamate yielding the products. proton shuttle (general acid/base)
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Kohls D et al. (2000), Structure, 8, 35-46. The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase: implications for substrate channeling in a bifunctional enzyme. DOI:10.1016/s0969-2126(00)00078-2. PMID:10673422.

Step 1.

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Catalytic Residues Roles

Residue Roles
His82(81)A proton shuttle (general acid/base)

Chemical Components

Step 1.

Contributors

Alex Gutteridge, Craig Porter, Gemma L. Holliday