Related Experiment Video
Updated: Feb 24, 2026
12:11
Simultaneous Affinity Enrichment of Two Post-Translational Modifications for Quantification and Site Localization
Published on: February 27, 2020
7.3K
Improved Method for the Identification and Validation of Allosteric Sites.
Kun Song1, Xinyi Liu1, Wenkang Huang1
1Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University, School of Medicine , Shanghai, 200025, China.
Journal of Chemical Information and Modeling
|August 22, 2017
Summary
AllositePro predicts allosteric sites in proteins by analyzing pocket features and perturbations. This novel method aids in identifying allosteric drug targets, as demonstrated by its application to cyclin-dependent kinase 2 (CDK2).
Area of Science:
- Structural biology
- Computational chemistry
- Drug discovery
Background:
- Allosteric regulation offers precise control over protein function through modulators binding to distinct sites.
- Allosteric modulators possess high selectivity and low toxicity due to the structural diversity of allosteric sites.
- Identifying allosteric sites is crucial for developing novel allosteric drugs, a rapidly growing area in pharmaceutical research.
Purpose of the Study:
- To develop and present AllositePro, a computational method for predicting allosteric sites in proteins.
- To evaluate the performance of AllositePro against existing methods for allosteric site identification.
- To demonstrate the utility of AllositePro in identifying novel allosteric sites for drug discovery applications.
Main Methods:
- AllositePro integrates protein pocket features with perturbation analysis to predict allosteric sites.
- The method's performance was benchmarked against other available allosteric site prediction tools.
- A novel allosteric site in cyclin-dependent kinase 2 (CDK2) was predicted using AllositePro.
Main Results:
- AllositePro demonstrated superior performance compared to existing allosteric site prediction methods.
- A previously unknown allosteric site in CDK2 was successfully predicted by AllositePro.
- The predicted allosteric site in CDK2 was experimentally validated using a site-directed mutagenesis assay.
Conclusions:
- AllositePro provides an effective computational strategy for identifying protein allosteric sites.
- The method holds significant potential as a valuable tool in the field of allosteric drug discovery.
- Successful validation of a novel CDK2 allosteric site underscores the practical applicability of AllositePro.
Related Concept Videos
01:19Allosteric Proteins-ATCase
6.7K
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...
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...
6.7K
01:08Allosteric Regulation
63.7K
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...
63.7K
00:49Ligand Binding and Linkage
5.7K
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...
5.7K
01:30Enzyme Inhibition
93.3K
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.
93.3K
01:49Conserved Binding Sites
5.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.2K
01:58Cooperative Allosteric Transitions
9.1K
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...
9.1K