Aromatic-amino-acid transaminase
Tyrosine (aromatic) aminotransferase (TATase) is a well-characterized Fold Type I PLP-dependent enzyme that has natural specificity for the aromatic amino acids tyrosine, phenylalanine, and tryptophan, as well as for the dicarboxylic amino acids aspartate and glutamate.
Reference Protein and Structure
- Sequence
-
P95468
(2.6.1.57)
(Sequence Homologues)
(PDB Homologues)
- Biological species
-
Paracoccus denitrificans (Bacteria)
- PDB
-
1ay4
- AROMATIC AMINO ACID AMINOTRANSFERASE WITHOUT SUBSTRATE
(2.33 Å)
- Catalytic CATH Domains
-
3.40.640.10
(see all for 1ay4)
- Cofactors
- Pyridoxal 5'-phosphate(2-) (1)
Enzyme Reaction (EC:2.6.1.57)
+
→
+
Alternative enzyme names: ArAT, Aromatic amino acid aminotransferase, Aromatic aminotransferase,
Enzyme Mechanism
Introduction
Transamination occurs in two steps: the amine group of the substrate amino acid residue (the amino donor) undergoes a transaldimination with PLP, liberating Lys and resulting in the oxo-acid product. Then the second substrate accepts the amino group and lysine is reattached to the PLP cofactor in a second transaldinination reaction.
Catalytic Residues Roles
| UniProt | PDB* (1ay4) | ||
| Asp208 | Asp222(208)A | N1 of PLP forms an ion pair with the carboxylate of Asp222, this acts to stabilise the PLP intermediates. | electrostatic stabiliser |
| Lys243 | Lys258(243)A | Is covalently bound to the PLP in the ground state of the enzyme. Acts as a general acid/base and is a catalytic nucleophile in the product release steps of the reaction. | covalent catalysis, proton shuttle (general acid/base) |
| Ala210, Trp127 | Ala224(210)A, Trp140(127)A | The pyridine ring is sandwiched by the side-chains of Trp140 and Ala224 and is nearly parallel to the indole ring of Trp140. These interactions serve to hold the free PLP intermediates in the correct position for the rest of the reaction to occur. | steric role |
*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
- Moreno MA et al. (2014), Acta Crystallogr F Struct Biol Commun, 70, 583-587. Structure of tyrosine aminotransferase fromLeishmania infantum. DOI:10.1107/s2053230x14007845. PMID:24817714.
- Okamoto A et al. (1999), Biochemistry, 38, 1176-1184. The Active Site ofParacoccus denitrificansAromatic Amino Acid Aminotransferase Has Contrary Properties: Flexibility and Rigidity†,‡. DOI:10.1021/bi981921d. PMID:9930977.
- Okamoto A et al. (1998), J Mol Biol, 280, 443-461. Crystal structures of Paracoccus denitrificans aromatic amino acid aminotransferase: a substrate recognition site constructed by rearrangement of hydrogen bond network. DOI:10.1006/jmbi.1998.1869. PMID:9665848.
Catalytic Residues Roles
| Residue | Roles |
|---|---|
| Trp140(127)A | steric role |
| Asp222(208)A | electrostatic stabiliser |
| Lys258(243)A | covalent catalysis |
| Ala224(210)A | steric role |
| Lys258(243)A | proton shuttle (general acid/base) |