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Related Concept Videos

Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Allosteric Regulation01:08

Allosteric Regulation

Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
Allosteric Regulation01:08

Allosteric Regulation

Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...

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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Allosteric cooperativity in protein kinase A.

Larry R Masterson1, Alessandro Mascioni, Nathaniel J Traaseth

  • 1Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 8, 2008
PubMed
Summary
This summary is machine-generated.

Allosteric signaling in protein kinase A involves long-range communication. A mutation disrupted this network, impacting ligand binding cooperativity and offering insights into other protein kinases.

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Area of Science:

  • Biochemistry and Molecular Biology
  • Protein Dynamics and Allostery
  • Enzymology

Background:

  • Allosteric signaling in proteins relies on conserved residues for long-range communication, often initiated by ligand binding.
  • Understanding these communication pathways is crucial for deciphering protein function and regulation.

Purpose of the Study:

  • To map the allosteric network within the catalytic subunit of protein kinase A (PKA).
  • To investigate the role of specific residues in mediating allosteric cooperativity.
  • To explore the impact of mutations on PKA's allosteric signaling mechanism.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy was employed to analyze the allosteric network.
  • Conformational states (apo, intermediate, closed) were studied in relation to ligand binding.
  • Site-directed mutagenesis (Y204A) was used to probe the network's function.

Main Results:

  • Positive allosteric cooperativity in PKA is generated by nucleotide and substrate binding across different conformational states.
  • A single mutation (Y204A) disrupts the identified allosteric network.
  • This mutation decouples the cooperativity of ligand binding, highlighting the network's importance.

Conclusions:

  • The study successfully maps the allosteric network in protein kinase A, revealing key communication pathways.
  • The findings demonstrate that conserved residues are critical for maintaining allosteric cooperativity.
  • Given PKA's role as a kinome prototype, these results provide a potential paradigm for understanding allosteric coupling in other protein kinases.