4-aminobutyrate transaminase
4-aminobutyrate aminotransferase is a class III pyridoxal-phosphate-dependent aminotransferase. The enzyme catalyses the conversion of 4-aminobutanoate and 2-oxoglutarate into succinate semialdehyde and L-glutamate.
Reference Protein and Structure
- Sequence
-
P80147
(2.6.1.19, 2.6.1.22)
(Sequence Homologues)
(PDB Homologues)
- Biological species
-
Sus scrofa (pig)
- PDB
-
1ohv
- 4-AMINOBUTYRATE-AMINOTRANSFERASE FROM PIG
(2.3 Å)
- Catalytic CATH Domains
-
3.40.640.10
(see all for 1ohv)
- Cofactors
- Di-mu-sulfido-diiron(2+) (1), Pyridoxal 5'-phosphate(2-) (1)
Enzyme Reaction (EC:2.6.1.19)
+
→
+
Alternative enzyme names: 4-aminobutyrate aminotransferase, 4-aminobutyrate--2-ketoglutarate aminotransferase, 4-aminobutyrate--2-oxoglutarate aminotransferase, 4-aminobutyrate-2-oxoglutarate transaminase, 4-aminobutyric acid 2-ketoglutaric acid aminotransferase, 4-aminobutyric acid aminotransferase, Beta-alanine aminotransferase, Beta-alanine--oxoglutarate aminotransferase, Beta-alanine--oxoglutarate transaminase, Gamma-aminobutyrate aminotransaminase, Gamma-aminobutyrate transaminase, Gamma-aminobutyrate:alpha-oxoglutarate aminotransferase, Gamma-aminobutyrate--alpha-ketoglutarate aminotransferase, Gamma-aminobutyrate--alpha-ketoglutarate transaminase, Gamma-aminobutyric acid aminotransferase, Gamma-aminobutyric acid pyruvate transaminase, Gamma-aminobutyric acid transaminase, Gamma-aminobutyric acid--2-oxoglutarate transaminase, Gamma-aminobutyric acid--alpha-ketoglutarate transaminase, Gamma-aminobutyric acid--alpha-ketoglutaric acid aminotransferase, Gamma-aminobutyric transaminase, GABA aminotransferase, GABA transaminase, GABA transferase, GABA--2-oxoglutarate aminotransferase, GABA--2-oxoglutarate transaminase, GABA--alpha-ketoglutarate aminotransferase, GABA--alpha-ketoglutarate transaminase, GABA--alpha-ketoglutaric acid transaminase, GABA--alpha-oxoglutarate aminotransferase, GABA--oxoglutarate aminotransferase, GABA--oxoglutarate transaminase, Aminobutyrate aminotransferase, Aminobutyrate transaminase, Glutamate--succinic semialdehyde transaminase, Gamma-amino-N-butyrate transaminase, GabT,
Enzyme Mechanism
Introduction
The catalytic mechanism of GABA-AT is usually divided into two parts. In the first half reaction, the natural substrate GABA is converted to succinic semialdehyde and it involves the conversion of PLP to pyridoxamine phosphate (PMP). The PMP molecule in the active site is then bound to the enzyme again during the second half reaction.
Catalytic Residues Roles
| UniProt | PDB* (1ohv) | ||
| Phe217 | Phe189A | Ensures that the PLP cofactor doesn't rotate in the active site once cleaved from the enzyme. | steric role |
| Asp326 | Asp298A | Forms a hydrogen bond with the N of the ring in PLP which helps the cofactor act as an electron sink during the course of the reaction. | electrostatic stabiliser |
| Lys357 | Lys329A | In the ground state of the enzyme this residue is covalently attached to the PLP cofactor. It also acts as a general acid/base as well as a catalytic nucleophile. | covalent catalysis, proton shuttle (general acid/base) |
| Thr381 | Thr353B | Hydrogen bonds with the PLP cofactor, helping to stabilise the reactive intermediates formed during the course of the reaction. | electrostatic stabiliser |
*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
- Gökcan H et al. (2016), Proteins, 84, 875-891. Molecular dynamics simulations of apo, holo, and inactivator bound GABA-at reveal the role of active site residues in PLP dependent enzymes. DOI:10.1002/prot.24991. PMID:26800298.
- Lee H et al. (2015), J Am Chem Soc, 137, 2628-2640. Mechanism of inactivation of γ-aminobutyric acid aminotransferase by (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115). DOI:10.1021/ja512299n. PMID:25616005.
- Lee H et al. (2015), ACS Chem Biol, 10, 2087-2098. Mechanism of Inactivation of GABA Aminotransferase by (E)- and (Z)-(1S,3S)-3-Amino-4-fluoromethylenyl-1-cyclopentanoic Acid. DOI:10.1021/acschembio.5b00212. PMID:26110556.
- Storici P et al. (2004), J Biol Chem, 279, 363-373. Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin. DOI:10.1074/jbc.M305884200. PMID:14534310.
Catalytic Residues Roles
| Residue | Roles |
|---|---|
| Lys329A | proton shuttle (general acid/base), covalent catalysis |
| Phe189A | steric role |
| Asp298A | electrostatic stabiliser |
| Thr353B | electrostatic stabiliser |