Related Experiment Video

Updated: Dec 19, 2025

Concanavalin A-Based Sedimentation Assay to Measure Substrate Binding of Glucan Phosphatases
09:07

Concanavalin A-Based Sedimentation Assay to Measure Substrate Binding of Glucan Phosphatases

Published on: December 23, 2022

1.7K

O-GlcNAcase: Emerging Mechanism, Substrate Recognition and Small-Molecule Inhibitors

Ahmed A Elbatrawy1,2, Eun Ju Kim3, Ghilsoo Nam1,2

  • 1Center for Neuro-Medicine Brain Science Institute, Korea Institutes of Science and Technology, Seoul, 02792 (Republic of, Korea.

Chemmedchem
|June 5, 2020
PubMed

Insights

O-GlcNAcylation regulates cell cycles but is linked to diseases. This review details human O-GlcNAcase structure and function, and explores small-molecule inhibitors for therapeutic potential.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Glycobiology

Background:

  • O-GlcNAcylation is a dynamic post-translational modification regulating nucleocytoplasmic proteins.
  • This process is controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
  • Dysregulated O-GlcNAcylation is implicated in diseases like cancer, diabetes, and neurodegeneration.

Purpose of the Study:

  • To review recent structural insights into human O-GlcNAcase and its isoforms.
  • To elucidate the catalytic mechanism and substrate recognition of OGA.
  • To provide an updated overview of small-molecule OGA inhibitors, focusing on their structure, selectivity, and cellular applications.

Main Methods:

  • Structural analysis of human O-GlcNAcase.
  • Biochemical assays to study catalytic mechanism and substrate binding.
  • Review of literature on small-molecule OGA inhibitors.

Main Results:

  • Recent advancements in understanding human O-GlcNAcase structure and isoforms.
  • Detailed insights into OGA's catalytic mechanism and substrate recognition.
  • Comprehensive summary of carbohydrate and noncarbohydrate OGA inhibitors, including their binding modes and selectivity.

Conclusions:

  • Understanding OGA structure is crucial for designing selective inhibitors.
  • Small-molecule inhibitors offer potential for probing O-GlcNAcylation in cellular contexts.
  • Targeting OGA may hold therapeutic promise for diseases linked to O-GlcNAcylation dysregulation.
Keywords:
O-GlcNAcaseO-GlcNAcylationOGAglycoside hydrolase inhibitorssubstrate-assisted catalysis.

More Related Videos

Spectrophotometric Methods for the Study of Eukaryotic Glycogen Metabolism07:59

Spectrophotometric Methods for the Study of Eukaryotic Glycogen Metabolism

Published on: August 19, 2021

4.3K
Author Spotlight: Integrating Biochemical Functions of β-Glucanases and Peroxidase Enzymes in Wheat-RWA Interaction10:26

Author Spotlight: Integrating Biochemical Functions of β-Glucanases and Peroxidase Enzymes in Wheat-RWA Interaction

Published on: July 26, 2024

1.1K

Related Concept Videos

Enzyme Inhibition01:30

Enzyme Inhibition

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.
90.1K
Enzymes02:34

Enzymes

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...
91.8K
Introduction to Mechanisms of Enzyme Catalysis01:13

Introduction to Mechanisms of Enzyme Catalysis

For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes...
10.3K
Oligosaccharide Assembly01:24

Oligosaccharide Assembly

Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
3.4K
Indirect-Acting Cholinergic Agonists: Mechanism of Action01:18

Indirect-Acting Cholinergic Agonists: Mechanism of Action

Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
2.4K
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
451