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

Cytoskeletal Linker Proteins - Plakins01:09

Cytoskeletal Linker Proteins - Plakins

Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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 the...

You might also read

Related Articles

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

Sort by
Same author

Simultaneous TCR and IL-2 agonism selectively enhances epitope-specific CD8 T-cell responses during chronic viral infection.

Journal of virology·2026
Same author

A comprehensive discovery platform for ELOVL1 small-molecule inhibitors targeting very long-chain fatty acid synthesis in adrenoleukodystrophy.

The Journal of biological chemistry·2026
Same author

HIV- and cytomegalovirus-specific human memory CD8+ T cells are activated and expanded independent of co-stimulatory signaling by T-cell receptor-specific immunotherapeutics.

Journal of immunology (Baltimore, Md. : 1950)·2026
Same author

T-cell receptor/CD28-targeted immunotherapeutics selectively drive naive T-cell expansion to generate functional HIV-specific responses.

Journal of virology·2025
Same author

Tilting the Scales toward EGFR Mutant Selectivity: Expanding the Scope of Bivalent "Type V" Kinase Inhibitors.

Journal of medicinal chemistry·2024
Same author

From hit to vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation.

Science advances·2024

Related Experiment Video

Updated: Jul 10, 2026

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
14:34

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English

Published on: April 3, 2026

Selectivity-determining residues in Plk1.

Michael Kothe1, Darcy Kohls, Simon Low

  • 1Pfizer Global Research and Development, Research Technology Center, 620 Memorial Drive, Cambridge, MA 02139, USA.

Chemical Biology & Drug Design
|November 17, 2007
PubMed
Summary

Polo-like kinase 1 (PLK1) is crucial for cell cycle control and cancer. This study reveals the crystal structure of PLK1 with the inhibitor BI 2536, offering insights into drug design for cancer therapy.

More Related Videos

Understanding the Development of Compensatory Pathways in a Mutant Malaria Parasite Harbouring Hypomorphic Allele of Plant-Like Kinases
09:13

Understanding the Development of Compensatory Pathways in a Mutant Malaria Parasite Harbouring Hypomorphic Allele of Plant-Like Kinases

Published on: November 22, 2024

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
06:50

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

Published on: January 26, 2024

Related Experiment Videos

Last Updated: Jul 10, 2026

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
14:34

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English

Published on: April 3, 2026

Understanding the Development of Compensatory Pathways in a Mutant Malaria Parasite Harbouring Hypomorphic Allele of Plant-Like Kinases
09:13

Understanding the Development of Compensatory Pathways in a Mutant Malaria Parasite Harbouring Hypomorphic Allele of Plant-Like Kinases

Published on: November 22, 2024

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions
06:50

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

Published on: January 26, 2024

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Polo-like kinase 1 (PLK1) is a key regulator of cell cycle progression.
  • Overexpression of PLK1 is linked to oncogenesis, making it a target for cancer intervention.
  • BI 2536 is a potent and selective PLK1 inhibitor in clinical trials.

Purpose of the Study:

  • To determine the co-crystal structure of Polo-like kinase 1 (PLK1) in complex with the inhibitor BI 2536.
  • To elucidate structural features contributing to BI 2536's potency and selectivity.
  • To provide a basis for structure-based drug design of PLK1 inhibitors.

Main Methods:

  • X-ray crystallography to obtain the co-crystal structure of PLK1 and BI 2536.
  • Analysis of the co-crystal structure to identify key interactions.
  • Evaluation of selectivity data for BI 2536 and related compounds.

Main Results:

  • The co-crystal structure of PLK1 with BI 2536 was determined.
  • The methoxy group of BI 2536 was identified as a critical specificity determinant.
  • A small pocket formed by Leu 132 in the PLK1 hinge region accommodates the methoxy group, enhancing selectivity against non-PLK kinases.

Conclusions:

  • The structure-based insights explain the high potency and selectivity of BI 2536.
  • The findings provide a framework for designing novel, specific PLK1 inhibitors for cancer therapy.
  • Understanding these interactions is crucial for developing targeted cancer treatments.