Phosphoserine transaminase

 

A pyridoxal-phosphate-dependent enzyme. It catalyses the second step in the phosphorylated pathway of serine biosynthesis in Escherichia coli (the reversible conversion of 3-phosphohydroxypyruvate to phosphoserine). It also catalyses the third step in the biosynthesis of the coenzyme pyridoxal 5'-phosphate in E. coli (the reversible conversion of 3-hydroxy-2-oxo-4-phosphonooxybutanoate to phosphohydroxythreonine).

 

Reference Protein and Structure

Sequence
P23721 UniProt (2.6.1.52) IPR022278 (Sequence Homologues) (PDB Homologues)
Biological species
Escherichia coli K-12 (Bacteria) Uniprot
PDB
1bjo - THE STRUCTURE OF PHOSPHOSERINE AMINOTRANSFERASE FROM E. COLI IN COMPLEX WITH ALPHA-METHYL-L-GLUTAMATE (2.8 Å) PDBe PDBsum 1bjo
Catalytic CATH Domains
3.40.640.10 CATHdb (see all for 1bjo)
Cofactors
Pyridoxal 5'-phosphate(2-) (1)
Click To Show Structure

Enzyme Reaction (EC:2.6.1.52)

O-phosphonato-L-serine(2-)
CHEBI:57524ChEBI
+
2-oxoglutarate(2-)
CHEBI:16810ChEBI
→
L-glutamate(1-)
CHEBI:29985ChEBI
+
3-phosphonatooxypyruvate(3-)
CHEBI:18110ChEBI
Alternative enzyme names: 3-phosphoserine aminotransferase, L-phosphoserine aminotransferase, PSAT, Hydroxypyruvic phosphate--glutamic transaminase, Phosphohydroxypyruvate transaminase, Phosphohydroxypyruvic--glutamic transaminase, Phosphoserine aminotransferase, 3-O-phospho-L-serine:2-oxoglutarate aminotransferase, SerC, PdxC, 3PHP transaminase,

Enzyme Mechanism

Introduction

The first chemical step in the catalytic mechanism is the transfer, in the Michaelis complex, of a proton of the charged substrate amino group to the unprotonated imine nitrogen of the internal Schiff base, followed by nucleophilic attack of the substrate amino group on the C4’ carbon atom of the cofactor, resulting in formation of the external aldimine intermediate between PLP and the substrate. Subsequently, deprotonation of the alpha-carbon atom of the substrate followed by reprotonation at the C4′ carbon atom of PLP to produce the ketimine intermediate take place. Finally its hydrolysis to the oxo acid product and release of that complete the catalytic half-reaction.

Catalytic Residues Roles

UniProt PDB* (1bjo)
Asp174 Asp174(172)A Forms a hydrogen bond to the nitrogen of the protonated pyridine nitrogen of PLP, stabilising the reaction intermediates. electrostatic stabiliser, steric role
Trp102 Trp102(100)A The PLP cofactor pyridine ring forms favourable stacking interactions with the indole ring of Trp102, helping to locate and stabilise the intermediates of the reaction. electrostatic stabiliser, steric role
Lys198 Lys198(196)A Acts as the catalytic nucleophile and general acid/base. At the start of the reaction it is covalently bound to the PLP cofactor. covalent catalysis, 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. Hester G et al. (1999), J Mol Biol, 286, 829-850. Crystal structure of phosphoserine aminotransferase from Escherichia coli at 2.3 Å resolution: comparison of the unligated enzyme and a complex with α-methyl-l-glutamate. DOI:10.1006/jmbi.1998.2506. PMID:10024454.
  2. Singh RK et al. (2016), Biochim Biophys Acta, 1860, 1508-1518. Structural investigation and inhibitory response of halide on phosphoserine aminotransferase from Trichomonas vaginalis. DOI:10.1016/j.bbagen.2016.04.013. PMID:27102280.
  3. Mishra V et al. (2012), Amino Acids, 43, 483-491. Role of conserved active site tryptophan-101 in functional activity and stability of phosphoserine aminotransferase from an enteric human parasite. DOI:10.1007/s00726-011-1105-x. PMID:22038178.
  4. Drewke C et al. (1996), FEBS Lett, 390, 179-182. 4-O-phosphoryl-L-threonine, a substrate of the pdxC(serC) gene product involved in vitamin B6 biosynthesis. PMID:8706854.

Step 1.

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Catalytic Residues Roles

Residue Roles
Lys198(196)A covalent catalysis, proton shuttle (general acid/base)
Trp102(100)A electrostatic stabiliser
Asp174(172)A electrostatic stabiliser
Trp102(100)A steric role
Asp174(172)A steric role

Chemical Components

Step 1.

Contributors

Atlanta Cook, Craig Porter, Gemma L. Holliday