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Related Concept Videos

Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
Induced-fit Model01:13

Induced-fit Model

Most chemical reactions in cells require enzymes—biological catalysts that speed up the reaction without being consumed or permanently changed. They reduce the activation energy needed to convert the reactants into products. Enzymes are proteins, that usually work by binding to a substrate—a reactant molecule that they act upon.
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical characteristics of...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

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...
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 a mild...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

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...

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Related Experiment Video

Updated: Jul 11, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Substrate specificity of cyclins determined by electrostatics.

Hui Jun Lee1, Gek Huey Chua, Arun Krishnan

  • 1Bioinformatics Institute, Matrix, Singapore.

Cell Cycle (Georgetown, Tex.)
|September 25, 2007
PubMed
Summary

Cyclin B1 escapes regulation by CDK inhibitors due to specific charged residues in its cyclin groove. This explains differential substrate recognition and has implications for cancer therapy.

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Last Updated: Jul 11, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

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Published on: August 29, 2015

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Structural Biology

Background:

  • Cyclin-dependent kinases (CDKs) regulate cell cycle and transcription via phosphorylation.
  • CDK complexes exhibit substrate specificity, influenced by the cyclin groove, but the mechanism is unclear.
  • Cyclins A2, E1, and B1, though similar, show distinct interactions with substrate-derived peptides.

Purpose of the Study:

  • To elucidate the mechanism of differential substrate recognition among cyclins A2, E1, and B1.
  • To explain why cyclin B1 is not inhibited by p21 family of CDK inhibitors, unlike cyclins A2 and E1.
  • To identify the structural basis for cyclin B1's escape from CDKI regulation.

Main Methods:

  • Analysis of electrostatic potentials of cyclins A2, E1, and B1.
  • Comparison of cyclin-binding motifs (ZRXL) in substrate/inhibitor peptides.
  • Computational energetics of peptide-cyclin binding.
  • Identification of conserved charged residues and suggested mutations.

Main Results:

  • Cyclins A2 and E1 possess anionic regions in the cyclin groove that facilitate peptide binding and inhibition.
  • Cyclin B1 has cationic regions at homologous positions, abrogating peptide binding and thus inhibition.
  • Computed energetics confirmed the role of electrostatic interactions in differential binding.
  • Specific charged residues, conserved across species, dictate the differential binding and inhibition.

Conclusions:

  • The electrostatic surface potential of the cyclin groove is a key determinant of substrate/inhibitor peptide binding.
  • Cyclin B1's unique cationic surface prevents inhibition by p21 family CDKIs, explaining its distinct regulatory behavior.
  • Understanding these specificity mechanisms is crucial for developing targeted cancer therapies that exploit CDK deregulation.