Enzyme
1.1.1.95 - Phosphoglycerate dehydrogenase
Alternative Name(s)
- 3-phosphoglycerate dehydrogenase.
- D-3-phosphoglycerate dehydrogenase.
- Glycerate 3-phosphate dehydrogenase.
- Phosphoglycerate oxidoreductase.
- Glycerate-1,3-phosphate dehydrogenase.
- Phosphoglyceric acid dehydrogenase.
- 3PHP reductase.
- Alpha-KG reductase.
- PGDH.
- Alpha-phosphoglycerate dehydrogenase.
- 3-phosphoglyceric acid dehydrogenase.
Catalytic Activity
(2R)-3-phosphoglycerate + NAD(+) = 3-phosphooxypyruvate + H(+) + NADH
Cofactors
There are no Cofactors for this Enzyme
Reaction Mechanism
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.
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
| AA | Uniprot | Uniprot Resid | PDB | PDB Resid |
|---|---|---|---|---|
| His | P0A9T0 | 292 | 1psd | 291 |
| Glu | P0A9T0 | 269 | 1psd | 268 |
Step Components
inferred reaction step, hydride transfer, aromatic bimolecular nucleophilic addition, proton transfer, native state of enzyme regenerated, overall reactant used, overall product formed
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.
The products of the reaction.
Reaction Parameters
-
Kinetic Parameters
Organism KM Value [mM] Substrate Comment Arabidopsis thaliana 0.000017 2-oxoglutarate pH 6.0, 25°C Mycobacterium tuberculosis 0.14 2-oxoglutarate mutant enzyme R72L, pH 7.0, temperature not specified in the publication Entamoeba histolytica 0.216 3-phospho-D-glycerate mutant enzyme K263A, at pH 9.0 and 25°C Escherichia coli 0.5 3-phospho-D-glycerate pH and temperature not specified in the publication Marchantia polymorpha 51 3-phospho-D-glycerate pH 9.0, temperature not specified in the publication -
Temperature
Organism Temperature Range Comment Bombyx mori 20 - 50 at temperatures of 20-50°C, the activity of the enzyme is greater than 80% of maximal activity -
pH
Organism pH Range Comment Bombyx mori 4 - 9 pH 4.0: about 82% of maximal activity, pH 9.0: about 80% of maximal activity Glycine max 5 - 7.8 about 50% of activity maximum at pH 5 and 7.8, NADH oxidation Mycobacterium tuberculosis 5.2 - 5.7 at approximately pH 5.7 the activity starts increasing again and reaches a new optimum at approximately pH 5.2 before decreasing once again Escherichia coli 5.5 - 8.5 Tris buffer and phosphate buffer Entamoeba histolytica 6.5 - 8 enzymatic activity decreases below pH 6.5
Associated Proteins
Citations
- [Phosphoglycerate dehydrogenase deficiency in a child].
- Designing Cyclic-Constrained Peptides to Inhibit Human Phosphoglycerate Dehydrogenase.
- Biochemical and cellular studies of three human 3-phosphoglycerate dehydrogenase variants responsible for pathological reduced L-serine levels.
- Inhibition of phosphoglycerate dehydrogenase induces ferroptosis and overcomes enzalutamide resistance in castration-resistant prostate cancer cells.
- Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence.
- Low Phosphoglycerate Dehydrogenase Levels Drive Metastatic Dissemination.
- Mild phenotypes of phosphoglycerate dehydrogenase deficiency by a novel mutation of PHGDH gene: Case report and literature review.
- Identification of Novel Natural Inhibitors to Human 3-Phosphoglycerate Dehydrogenase (PHGDH) for Cancer Treatment.
- Inhibition of Phosphoglycerate Dehydrogenase Radiosensitizes Human Colorectal Cancer Cells under Hypoxic Conditions.
- Non-canonical phosphoglycerate dehydrogenase activity promotes liver cancer growth via mitochondrial translation and respiratory metabolism.
- Phosphoglycerate dehydrogenase positively regulates the proliferation of chicken muscle cells.