Phosphoglycerate dehydrogenase

 

3-phosphoglycerate dehydrogenase catalyses the oxidation of D-3-phosphoglycerate to 3-phosphohydroxypyruvate with concurrent reduction of NAD+ to NADH. This reaction is the first committed step in serine biosynthesis. In the following steps transamination of 3-phosphohydroxypyruvate with glutamate yields phosphoserine and the action of a phosphatase completes the biosynthesis. In prokaryotes and plants 3-phosphoglycerate dehydrogenase is inhibited by serine in an allosteric fashion.

 

Reference Protein and Structure

Sequence
P0A9T0 UniProt (1.1.1.95, 1.1.1.399) IPR006139 (Sequence Homologues) (PDB Homologues)
Biological species
Escherichia coli K-12 (Bacteria) Uniprot
PDB
1psd - THE ALLOSTERIC LIGAND SITE IN THE VMAX-TYPE COOPERATIVE ENZYME PHOSPHOGLYCERATE DEHYDROGENASE (2.75 Å) PDBe PDBsum 1psd
Catalytic CATH Domains
3.40.50.720 CATHdb (see all for 1psd)
Click To Show Structure

Enzyme Reaction (EC:1.1.1.95)

3-phosphonato-D-glycerate(3-)
CHEBI:58272ChEBI
+
NAD(1-)
CHEBI:57540ChEBI
→
3-phosphonatooxypyruvate(3-)
CHEBI:18110ChEBI
+
hydron
CHEBI:15378ChEBI
+
NADH(2-)
CHEBI:57945ChEBI
Alternative enzyme names: 3-phosphoglycerate dehydrogenase, 3-phosphoglyceric acid dehydrogenase, Alpha-phosphoglycerate dehydrogenase, D-3-phosphoglycerate dehydrogenase, D-3-phosphoglycerate:NAD(+) oxidoreductase, Glycerate 3-phosphate dehydrogenase, Glycerate-1,3-phosphate dehydrogenase, Phosphoglycerate oxidoreductase, Phosphoglyceric acid dehydrogenase, PGDH, 3-phosphoglycerate:NAD(+) 2-oxidoreductase, 3PHP reductase, Alpha-KG reductase, D- and L-HGA, PHGDH (gene name), SerA, SerA 3PG dehydrogenase,

Enzyme Mechanism

Introduction

3-phosphoglycerate utilises a charge-relay system involving His 292 and Glu 269. His 292 deprotonates the C2 hydroxyl group of 3-phosphoglycerate as a hydride ion is transferred from C2 to NAD+. Glu 269 functions to modify the pKa of His 292, allowing it to carry out its catalytic role.

Catalytic Residues Roles

UniProt PDB* (1psd)
His292 His292(291)A Deprotonates the C2 hydroxyl group as hydride is transferred from C2 to NAD. proton acceptor, proton donor
Glu269 Glu269(268)A Modifies the pKa of His 292, allowing it to carry out its role in catalysis. 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

proton transfer, hydride transfer, overall product formed, overall reactant used, aromatic bimolecular nucleophilic addition, inferred reaction step, native state of enzyme regenerated

References

  1. Schuller DJ et al. (1995), Nat Struct Biol, 2, 69-76. The allosteric ligand site in the Vmax-type cooperative enzyme phosphoglycerate dehydrogenase. DOI:10.1038/nsb0195-69. PMID:7719856.
  2. Birktoft JJ et al. (1983), J Biol Chem, 258, 472-482. The presence of a histidine-aspartic acid pair in the active site of 2-hydroxyacid dehydrogenases. X-ray refinement of cytoplasmic malate dehydrogenase. DOI:10.2210/pdb2mdh/pdb. PMID:6848515.
  3. Dubrow R et al. (1977), J Biol Chem, 252, 1539-1551. Mobile Agents as an Architectural Concept for Internet-based Distributed Applications - The WASP Project Approach. PMID:14154.

Step 1. His292 depronates the hydroxyl group of 3-phosphoglycerate. This is facilitated by Glu269. A hydride from the hydroxyl carbon of 3-phosphoglycerate is transferred to NAD+ in an aromatic bimolecular nucleophilic addition reaction.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Glu269(268)A electrostatic stabiliser
His292(291)A proton acceptor

Chemical Components

proton transfer, hydride transfer, overall product formed, overall reactant used, ingold: aromatic bimolecular nucleophilic addition

Step 2. In an inferred step His292 is deprotonated to regenerate the native state of the enzyme.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
His292(291)A proton donor

Chemical Components

proton transfer, inferred reaction step, native state of enzyme regenerated
Download: Image, Marvin File

Step 1. His292 depronates the hydroxyl group of 3-phosphoglycerate. This is facilitated by Glu269. A hydride from the hydroxyl carbon of 3-phosphoglycerate is transferred to NAD+ in an aromatic bimolecular nucleophilic addition reaction.

Step 2. In an inferred step His292 is deprotonated to regenerate the native state of the enzyme.

Products.

Contributors

Steven Smith, Gemma L. Holliday, Amelia Brasnett