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Related Concept Videos

Enzyme Inhibition01:30

Enzyme Inhibition

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Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
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Protein-protein Interfaces02:04

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Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
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Allosteric Regulation01:08

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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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Allosteric Proteins-ATCase01:19

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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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Protein-Drug Binding: Determination Methods01:22

Protein-Drug Binding: Determination Methods

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Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
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Updated: Jul 19, 2025

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
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Systematic Analysis of Covalent and Allosteric Protein Kinase Inhibitors.

Elena Xerxa1, Oliver Laufkötter1, Jürgen Bajorath1

  • 1LIMES Program Unit Chemical Biology and Medicinal Chemistry, Department of Life Science Informatics, B-IT, Rheinische Friedrich-Wilhelms-Universität, Friedrich-Hirzebruch-Allee 5/6, D-53115 Bonn, Germany.

Molecules (Basel, Switzerland)
|August 12, 2023
PubMed
Summary

Covalent protein kinase inhibitors (CPKIs) show increased potency, especially with specific warheads, but not necessarily broader activity. New allosteric PKIs (APKIs) were also identified for structure-based drug design.

Keywords:
X-ray structuresallosteric inhibitorsbinding sitescovalent inhibitorspotencypromiscuityprotein kinaseswarheads

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Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Structural Biology

Background:

  • Protein kinase inhibitors (PKIs) are crucial in drug discovery, with growing interest in allosteric (APKIs) and covalent (CPKIs) types for enhanced selectivity and potency.
  • Covalent PKIs (CPKIs) offer potential advantages like high potency and prolonged residence times, driving renewed research interest.

Conclusions:

  • CPKIs can offer substantial potency gains, particularly with specific warheads, without a universal increase in off-target activity.
  • The identification of novel APKIs, including covalent variants, provides opportunities for structure-based design of selective kinase inhibitors.