Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

6.4K
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...
6.4K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

8.6K
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...
8.6K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

2.6K
2.6K
Allosteric Regulation01:08

Allosteric Regulation

62.8K
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...
62.8K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

5.4K
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...
5.4K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

8.6K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
8.6K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Mass Spectrometry-Based Lipidomics in Coffee: Linking Lipid Transformation to Flavor Formation and Quality Control.

Foods (Basel, Switzerland)·2026
Same author

Identification of <i>IL7R</i> as a key genetic risk locus in childhood steroid-sensitive nephrotic syndrome and IgA nephropathy.

Frontiers in immunology·2026
Same author

Evaluating the Performance of Large Language Models for Breast Cancer Patient Education: A Comparative Study.

Journal of cancer education : the official journal of the American Association for Cancer Education·2026
Same author

Effects of <i>Allium mongolicum</i> Essential Oil on Meat Quality and Flavor-Related Free Amino Acids in Finishing Lambs.

Animals : an open access journal from MDPI·2026
Same author

Replacing Dietary Roughage with Barley Hay Affects Rumen Fermentation, Microbial Community, Serum Immune and Antioxidant Status in Sheep.

Animals : an open access journal from MDPI·2026
Same author

<i>Allium mongolicum</i> Regel-Mediated Rumen Microbiota Intervention Modulates Hepatic Metabolome to Reduce 4-Alkyl Branched-Chain Fatty Acids in Lamb <i>Longissimus Thoracis</i> Muscle.

Foods (Basel, Switzerland)·2026
Same journal

Nature's Anaerobic Toolkit: Glycyl Radical Enzymes and Their Expanding Functional and Mechanistic Diversity.

Biochemistry·2026
Same journal

Structural Bases for the Unconventional Activity of a Viroporin Channel.

Biochemistry·2026
Same journal

Targeting the WASF3 Regulatory Complex in Pancreatic Cancer Using Stapled Peptides.

Biochemistry·2026
Same journal

Thermodynamic and Allosteric Drivers of Stilbene-Mediated Noncompetitive Inhibition of Firefly Luciferase.

Biochemistry·2026
Same journal

Gut Bacterial 20-Hydroxysteroid Dehydrogenases Modify Endogenous Glucocorticoids and Corticosteroid Drugs.

Biochemistry·2026
Same journal

Single-Residue Mutation Switch Reconfigures the Hierarchical Structure and Assembly of Amphiphilic Protein Block Copolymers for Hydration Layer-Dominated Water-Responsive Actuation.

Biochemistry·2026
See all related articles
  1. Home
  3. Distal Mutations Rewire Allosteric Networks To Control Substrate Specificity In Ptp1b.
  1. Home
  3. Distal Mutations Rewire Allosteric Networks To Control Substrate Specificity In Ptp1b.

Related Experiment Video

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.6K

Distal Mutations Rewire Allosteric Networks to Control Substrate Specificity in PTP1B.

Xiaoyuan Wang1, Ryan M Anderson1, Jinchan Liu1

  • 1Department of Chemistry, Yale University, New Haven, Connecticut 06511, United States.

Biochemistry
|November 26, 2025

View abstract on PubMed

Summary
This summary is machine-generated.

Mutations at distal sites in Protein Tyrosine Phosphatase 1B (PTP1B) alter its substrate specificity by disrupting communication networks. This reveals new ways to control PTP1B activity for treating diseases like diabetes and obesity.

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

10.0K
Aip1p Dynamics Are Altered by the R256H Mutation in Actin
08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

8.3K

Related Experiment Videos

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.6K
Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

10.0K
Aip1p Dynamics Are Altered by the R256H Mutation in Actin
08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

8.3K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Protein Tyrosine Phosphatase 1B (PTP1B) is crucial for cellular signaling, with dysregulation linked to metabolic and oncologic diseases.
  • Allosteric regulation of PTP1B by distal sites is not well understood, limiting therapeutic targeting.

Purpose of the Study:

  • To investigate how mutations at four distal allosteric sites impact PTP1B's substrate specificity and enzymatic dynamics.
  • To elucidate the molecular mechanisms underlying allosteric regulation in PTP1B.

Main Methods:

  • Site-directed mutagenesis of PTP1B at Y153, I275, M282, and E297.
  • Enzymatic kinetic analyses using phosphotyrosine peptides and p-nitrophenylphosphate.
  • Solution Nuclear Magnetic Resonance (NMR) spectroscopy and microsecond molecular dynamics simulations.

Main Results:

  • Allosteric mutations significantly altered PTP1B's catalytic efficiency and substrate preference.
  • Mutations disrupted long-range communication networks, affecting helix coupling and active-site dynamics.
  • The E297A mutation most profoundly impacted the acid loop and allosteric communication.

Conclusions:

  • Distal mutations can reshape PTP1B's dynamic landscape, modulating substrate specificity.
  • The acid loop and helix α7 are key hubs for allosteric communication in PTP1B.
  • Understanding these dynamic networks offers a framework for controlling PTP1B activity therapeutically.