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

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

5.1K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.1K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

4.4K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.4K
Actin Filament Depolymerization01:19

Actin Filament Depolymerization

3.3K
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
3.3K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

3.0K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.0K

You might also read

Related Articles

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

Sort by
Same author

Geographical Variation in Bacterial Community Diversity and Composition of <i>Corythucha ciliata</i>.

Microorganisms·2025
Same author

Tetracycline changes the microbial assembly of Hyphantria cunea and reduces its fitness.

Environmental entomology·2025
Same author

Efficacy and safety of first-line chemotherapies for patients with advanced pancreatic ductal adenocarcinoma: A systematic review and network meta-analysis.

Heliyon·2024
Same author

Exploring the mechanism of C473D mutation on CDC25B causing weak binding affinity with CDK2/CyclinA by molecular dynamics study.

Journal of biomolecular structure & dynamics·2023
Same author

Scaffold-based selective SHP2 inhibitors design using core hopping, molecular docking, biological evaluation and molecular simulation.

Bioorganic chemistry·2020
Same author

Organic cation transporter 1 mediates the uptake of monocrotaline and plays an important role in its hepatotoxicity.

Toxicology·2013

Related Experiment Video

Updated: Oct 20, 2025

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

8.1K

Molecular dynamics study of CDC25BR492L mutant causing the activity decrease of CDC25B.

Hao-Xin Li1, Wen-Yu Yang2, Li-Peng Li1

  • 1Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, People's Republic of China.

Journal of Molecular Graphics & Modelling
|September 11, 2021
PubMed
Summary

The CDC25B R492L mutant significantly weakens binding with CDK2/CyclinA due to increased fluctuations in CDC25B regions and enhanced CDK2 self-interaction. Leu492 is identified as a key residue affecting this interaction.

Keywords:
CDC25B(R492L)-CDK2/CyclinA systemCDC25B(WT)-CDK2/CyclinA systemMolecular dynamics simulationPost-analysisRDOCKZDOCK

More Related Videos

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
05:56

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 2022

1.5K
High-resolution Imaging and Analysis of Individual Astral Microtubule Dynamics in Budding Yeast
10:23

High-resolution Imaging and Analysis of Individual Astral Microtubule Dynamics in Budding Yeast

Published on: April 20, 2017

9.7K

Related Experiment Videos

Last Updated: Oct 20, 2025

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

8.1K
Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
05:56

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 2022

1.5K
High-resolution Imaging and Analysis of Individual Astral Microtubule Dynamics in Budding Yeast
10:23

High-resolution Imaging and Analysis of Individual Astral Microtubule Dynamics in Budding Yeast

Published on: April 20, 2017

9.7K

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Structural Biology

Background:

  • Cell division cycle 25B (CDC25B) regulates cell cycle progression.
  • The CDC25B R492L mutant exhibits a ~100-fold reduction in phosphatase intermediate formation rate.
  • The molecular basis for weakened CDC25B R492L binding to CDK2/CyclinA remains unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms behind the reduced binding affinity of the CDC25B R492L mutant to CDK2/CyclinA.
  • To investigate the structural dynamics and interactions within the CDC25B-CDK2/CyclinA complex.
  • To identify key residues influencing the binding stability.

Main Methods:

  • 3D structure optimization of CDC25BWT-CDK2/CyclinA and CDC25BR492L-CDK2/CyclinA systems using ZDOCK and RDOCK.
  • Validation of docking structures using five independent methods.
  • Molecular dynamics simulations to analyze system dynamics and interactions.
  • Post-analysis of simulation trajectories to assess residue fluctuations and complex stability.

Main Results:

  • The CDC25BR492L mutant system exhibited high fluctuations in CDC25B's remote docking site (Arg488-Tyr497) and second active site (Lys538-Arg544).
  • These fluctuations led to weakened interactions between CDC25BR492L and CDK2.
  • CDK2 displayed slightly decreased fluctuations in specific regions (Asp38-Glu42, Asp206-Asp210) and enhanced self-interaction, maintaining its stability.
  • Leu492 of CDC25B was identified as a critical residue impacting the binding of CDC25BR492L to CDK2.

Conclusions:

  • The study provides a molecular understanding of the weak interactions between CDC25BR492L and CDK2.
  • Increased structural flexibility in specific CDC25B regions and altered CDK2 self-interaction contribute to the mutant's reduced binding affinity.
  • Leu492 is a key determinant of the CDC25B-CDK2 interaction stability.