The Mechanism of Velocity Modulated Allosteric Regulation in D-3-Phosphoglycerate Dehydrogenase

@article{AlRabiee1996TheMO,
  title={The Mechanism of Velocity Modulated Allosteric Regulation in D-3-Phosphoglycerate Dehydrogenase},
  author={Regina Al-Rabiee and Edward Joseph Lee and Gregory A Grant},
  journal={The Journal of Biological Chemistry},
  year={1996},
  volume={271},
  pages={13013 - 13017}
}
D-3-Phosphoglycerate dehydrogenase (PGDH) (EC) from Escherichia coli is an allosterically regulated enzyme of the Vmax type. It is a tetramer of identical subunits and each subunit is made up of three identifiable domains, the cofactor binding domain, the substrate binding domain, and the regulatory domain. Each subunit contacts two other subunits through adjacent cofactor binding domains and through adjacent regulatory domains. L-Serine, the physiological effector, inhibits catalytic activity… 

Figures and Tables from this paper

The Mechanism of Velocity Modulated Allosteric Regulation in −3-Phosphoglycerate Dehydrogenase SITE-DIRECTED MUTAGENESIS OF EFFECTOR BINDING SITE RESIDUES*
TLDR
Observations support the model that predicts that catalytic activity in −3-phosphoglycerate dehydrogenase is regulated by the movement of adjacent regulatory domains about a flexible hinge and that effector binding tethers the regulatory domains together producing a state that results in a stable, open active site cleft that is no longer able to promote catalysis.
Probing the Regulatory Domain Interface ofd-3-Phosphoglycerate Dehydrogenase with Engineered Tryptophan Residues*
TLDR
The observed fluorescence quenching of residues in the regulatory domains of d-3-phosphoglycerate dehydrogenase provide the first direct evidence for a conformational change in response to effector binding and provide a means to monitor the first step in the allosteric mechanism.
Removal of the tryptophan 139 side chain in Escherichia coli D-3-phosphoglycerate dehydrogenase produces a dimeric enzyme without cooperative effects.
TLDR
The results suggest that the magnitude of inhibition of activity at a particular active site is primarily dependent on serine binding to that subunit but that activity can be modulated in a cooperative manner by interaction with adjacent subunits.
Vmax regulation through domain and subunit changes. The active form of phosphoglycerate dehydrogenase.
TLDR
By comparing the inhibited with the uninhibited complex, it is possible to describe changes in conformation that are involved in the inhibitory signal transduction of serine.
The Contribution of Adjacent Subunits to the Active Sites ofd-3-Phosphoglycerate Dehydrogenase*
TLDR
Mutants of Trp-139′ show that this residue may play a role in stabilizing the catalytic center of the enzyme, and suggest a possible role for Trp -139′ in the cooperative interactions between subunits.
Cofactor Binding to Escherichia coli d-3-Phosphoglycerate Dehydrogenase Induces Multiple Conformations Which Alter Effector Binding*
TLDR
It is demonstrated that the presence of intrinsically bound NADH was responsible to a substantial degree for the lessening of both the positive and negative cooperativity of inhibitor binding as compared with that seen in the absence of NADH.
Multiconformational states in phosphoglycerate dehydrogenase.
TLDR
The structural and previous biochemical characterization of W139G PGDH suggests that the allosteric regulation of PGDH is mediated not only by changes occurring at the ACT domain interface but also by conformational changes at the interface encompassing residue W139.
The Effect of Hinge Mutations on Effector Binding and Domain Rotation in Escherichia coli D-3-Phosphoglycerate Dehydrogenase*
TLDR
The structure of G336V demonstrates that the minimal effect of l-serine binding leading to inhibition of enzyme activity requires a domain rotation of approximately only 6° in just two of the four subunits of the enzyme that are oriented diagonally across from each other in the tetramer.
Hybrid Tetramers Reveal Elements of Cooperativity in Escherichia coli d-3-Phosphoglycerate Dehydrogenase*
TLDR
Overall, the hybrid tetramers show that the positive cooperativity observed for serine binding is mediated across the nucleotide binding domain interface, and the negative cooperativity ismediated across the regulatory domain interface.
The relationship between effector binding and inhibition of activity in D‐3‐phosphoglycerate dehydrogenase
TLDR
Comparison of the data derived directly from binding stoichiometry to the binding constants determined from the best fit to the Adair equation, produce a close agreement, and reinforce the general validity of the derived binding constants.
...
...

References

SHOWING 1-10 OF 15 REFERENCES
A model for the regulation of D‐3‐phosphoglycerate dehydrogenase, a Vmax‐type allosteric enzyme
TLDR
The three‐dimensional structure of ePGDH provides a plausible model that is consistent with the binding and inhibition data and that suggests that catalysis and inhibition in this rare Vmax‐type allosteric enzyme is based on the movement of rigid domains about flexible hinges.
The allosteric ligand site in the Vmax-type cooperative enzyme phosphoglycerate dehydrogenase
TLDR
The crystal structure of the phosphoglycerate dehydrogenase from Eschehchia coli is unique among dehydrogenases and may play a key role in both catalysis and allosteric inhibition.
Structure of the regulatory complex of Escherichia coli IIIGlc with glycerol kinase
TLDR
The phosphorylation site of IIIGlc, His90, is buried in a hydrophobic environment formed by the active site region of IIiglc and a 3(10) helix of GK, suggesting that phosphorylated prevents IIIGLC binding to GK by directly disrupting protein-protein interactions.
Escherichia coli glycerol kinase: role of a tetramer interface in regulation by fructose 1,6-bisphosphate and phosphotransferase system regulatory protein IIIglc.
TLDR
Two mutant enzymes were identified and shown by DNA sequencing to contain the mutations alanine 65 to threonine (A65T) and aspartate 72 to asparagine (D72N), which alter the dimer-tetramer assembly reaction of the enzyme and the effect of FBP in increasing the molecular weight.
Isolation of a carboxyphosphate intermediate and the locus of acetyl-CoA action in the pyruvate carboxylase reaction.
TLDR
In the presence of K+ and at pH 9.5, the acetyl-CoA-independent activity of chicken liver pyruvate carboxylase approached 2% of theacetyl- CoA-stimulated rate, which represents a 30-fold increase on previously reported activity for this enzyme.
Physical location of the site for N-acetyl-L-glutamate, the allosteric activator of carbamoyl phosphate synthetase, in the 20-kilodalton COOH-terminal domain.
TLDR
Exhaustive tryptic digestion of photolabeled carbamoyl phosphate synthetase yielded a single radioactive peak, suggesting that the labeling is restricted to a single minimal tryptic peptide.
Electrostatic potential surface analysis of the transition state for AMP nucleosidase and for formycin 5'-phosphate, a transition-state inhibitor.
TLDR
The enzyme-stabilized transition state for AMP hydrolysis is characterized by new positive electrostatic potential in the adenine ring as a result of protonation by the enzyme, closely matched by the protonated pyrazole ring of formycin 5'-phosphate.
...
...