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

7.0K
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...
7.0K
Allosteric Regulation01:08

Allosteric Regulation

65.0K
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...
65.0K
Allosteric Regulation01:08

Allosteric Regulation

16.5K
16.5K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

6.0K
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...
6.0K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

2.8K
2.8K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

9.5K
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...
9.5K

You might also read

Related Articles

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

Sort by
Same author

Quantum-Centric Alchemical Free Energy Calculations.

Journal of chemical theory and computation·2026
Same author

An N-terminal amphipathic helix governs activity and conformational dynamics of Nramp metal transporters.

The Journal of biological chemistry·2026
Same author

An N-terminal amphipathic helix governs activity and conformational dynamics of Nramp metal transporters.

bioRxiv : the preprint server for biology·2026
Same author

Molecular Quantum Computations on a Protein.

Journal of chemical theory and computation·2026
Same author

Advancing Reproducibility and Open Data in Theoretical and Computational Chemistry.

Journal of chemical theory and computation·2026
Same author

Zinc-induced exposure of an LxL motif drives clathrin-mediated endocytosis of the zinc transceptor ZIP4.

The Journal of biological chemistry·2026
Same journal

Transcriptomic insights into epigenetic and immunomodulatory roles of nuclear histone genes in bladder cancer: A bioinformatics approach.

Advances in protein chemistry and structural biology·2026
Same journal

Investigating the immune-modulatory association of miRNAs in HPV-associated HNSCC individuals: A bioinformatics approach.

Advances in protein chemistry and structural biology·2026
Same journal

VISTA as a Double-Edged immune checkpoint molecule in cancer and autoimmunity.

Advances in protein chemistry and structural biology·2026
Same journal

Aptamers as immunomodulatory therapeutic alternatives targeting neglected tropical diseases (NTDs).

Advances in protein chemistry and structural biology·2026
Same journal

Peptides and peptidomimetics as immunomodulator agents targeting neglected tropical diseases.

Advances in protein chemistry and structural biology·2026
Same journal

Transcriptomic profiling reveals immune pathway dysregulation and key interferon-responsive genes in Systemic Lupus Erythematosus.

Advances in protein chemistry and structural biology·2026
See all related articles

Related Experiment Video

Updated: Apr 20, 2026

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
14:44

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR

Published on: December 16, 2013

10.2K

Studying allosteric regulation in metal sensor proteins using computational methods.

Dhruva K Chakravorty1, Kenneth M Merz2

  • 1Department of Chemistry, University of New Orleans, New Orleans, Louisiana, USA.

Advances in Protein Chemistry and Structural Biology
|December 3, 2014
PubMed
Summary
This summary is machine-generated.

Computational methods reveal a metal-ion-mediated hydrogen-bonding pathway that regulates DNA binding in metal-sensing proteins. This pathway acts as a switch, controlling protein function by locking DNA-binding conformations upon metal ion binding.

Keywords:
CzrAMolecular dynamicsTranscriptional repressoramberbonded modelhydrogen bondmetal ion mediated allosteryprotein-DNA interactionszinc ions

More Related Videos

Quantifying the Binding Interactions Between CuII and Peptide Residues in the Presence and Absence of Chromophores
11:38

Quantifying the Binding Interactions Between CuII and Peptide Residues in the Presence and Absence of Chromophores

Published on: April 5, 2022

3.1K
Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function
05:57

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Published on: April 26, 2024

1000

Related Experiment Videos

Last Updated: Apr 20, 2026

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
14:44

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR

Published on: December 16, 2013

10.2K
Quantifying the Binding Interactions Between CuII and Peptide Residues in the Presence and Absence of Chromophores
11:38

Quantifying the Binding Interactions Between CuII and Peptide Residues in the Presence and Absence of Chromophores

Published on: April 5, 2022

3.1K
Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function
05:57

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Published on: April 26, 2024

1000

Area of Science:

  • Biochemistry and Molecular Biology
  • Structural Biology
  • Computational Biology

Background:

  • The ArsR/SmtB family of proteins are crucial metal-sensing regulators involved in maintaining cellular metal homeostasis.
  • Understanding the allosteric regulation of DNA operator binding in these proteins is key to deciphering their regulatory mechanisms.
  • Staphylococcus aureus CzrA serves as a model system for investigating zinc-sensing transcriptional repressors.

Purpose of the Study:

  • To elucidate the mechanism of allosteric regulation of DNA operator binding in the ArsR/SmtB family of metal-sensing proteins.
  • To characterize the role of a metal ion-mediated hydrogen-bonding pathway (HBP) in this allosteric regulation.
  • To provide a molecular basis for metal ion-induced conformational changes and their impact on DNA binding.

Main Methods:

  • Utilized computational methods, including molecular dynamics (MD) simulations.
  • Integrated NMR-derived data to constrain MD simulations for accurate structure determination of metal ion-bound proteins.
  • Applied these methods to the zinc-sensing transcriptional repressor Staphylococcus aureus CzrA.

Main Results:

  • Identified a metal ion-mediated hydrogen-bonding pathway (HBP) that physically connects the metal-binding residue (His97) to the DNA-binding interface via the αR helix.
  • Quantified the allosteric coupling free energy associated with Zn(II) binding in CzrA (~6 kcal/mol).
  • Demonstrated that interprotomer hydrogen bond interactions are significantly stronger (~8 kcal/mol) at functional allosteric metal-binding sites compared to apo proteins, acting as a switch to lock DNA-binding conformation.

Conclusions:

  • The HBP is a conserved functional element in zinc-sensing transcription regulators, playing a dominant role in allosteric regulation of DNA binding.
  • Metal ion binding stabilizes the HBP, overcoming disorder in the apo state and enabling a switch to a DNA-binding conformation.
  • The computational approach integrating NMR data offers a robust method for studying metal ion-bound proteins and has broad applications in structural biology and protein design.