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Related Concept Videos

Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

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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...
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Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
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Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
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Enzymes02:34

Enzymes

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Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
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Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

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Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
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Allosteric Regulation01:08

Allosteric Regulation

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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...
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Updated: Jun 1, 2025

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach
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Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

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Binding-Site Switch for Protein Kinase CK2 Inhibitors.

Dylan Grenier1, Muriel Gelin2, Yinshan Yang2

  • 1Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de Lyon, Lyon, 69373, France.

Chemmedchem
|January 21, 2025
PubMed
Summary
This summary is machine-generated.

Researchers designed new CK2 inhibitors targeting the CK2α/CK2β interface. Several analogs maintained interface binding, with three compounds showing improved inhibition compared to CCH507.

Keywords:
Biolayer interferometryProtein kinase 2fragmentinhibitorsprotein-protein interface

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Identification of Kinase-substrate Pairs Using High Throughput Screening
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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Serine/threonine protein kinase CK2 (CK2) is a therapeutic target for cancer and viral infections.
  • CK2 inhibitors target the ATP-site, the αD pocket, or the CK2α/CK2β interface.

Purpose of the Study:

  • Design and evaluate novel CK2α/CK2β interface inhibitors based on the CCH507 structure.
  • Investigate structure-activity relationships for CK2 interface inhibition.

Main Methods:

  • Structure-based and fragment-based drug design approaches were employed.
  • Biolayer interferometry and fluorescence anisotropy assays assessed interface binding.
  • Bioluminescent ADP-Glo assay measured kinase inhibition potency.

Main Results:

  • Sixteen CCH507 analogs were synthesized and tested.
  • Seven compounds retained the ability to bind the CK2α/CK2β interface.
  • Three analogs demonstrated superior interface inhibition compared to CCH507.

Conclusions:

  • Novel CK2α/CK2β interface inhibitors were successfully developed.
  • Specific chemical modifications enhance CK2 interface binding and inhibition.
  • These findings provide a basis for developing more effective CK2-targeted therapies.