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Related Experiment Video

Updated: Jun 13, 2026

Purification of Human S100A12 and Its Ion-induced Oligomers for Immune Cell Stimulation

Purification of Human S100A12 and Its Ion-induced Oligomers for Immune Cell Stimulation

Published on: September 29, 2019

Phenothiazines inhibit S100A4 function by inducing protein oligomerization.

Vladimir N Malashkevich¹, Natalya G Dulyaninova, Udupi A Ramagopal

¹Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Proceedings of the National Academy of Sciences of the United States of America

|April 28, 2010

Summary

Trifluoperazine (TFP) disrupts cancer cell motility by binding to S100A4, forming oligomers that inhibit its interaction with myosin-IIA. This novel mechanism reveals TFP as a potential therapeutic agent for metastatic disease.

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Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

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Last Updated: Jun 13, 2026

Purification of Human S100A12 and Its Ion-induced Oligomers for Immune Cell Stimulation

Purification of Human S100A12 and Its Ion-induced Oligomers for Immune Cell Stimulation

Published on: September 29, 2019

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

Area of Science:

Biochemistry
Molecular Biology
Structural Biology

Background:

S100A4, a calcium-binding protein, is implicated in carcinoma cell motility and metastatic progression.
S100A4's role in metastasis makes it a potential therapeutic target.

Purpose of the Study:

To investigate the interaction between S100A4 and trifluoperazine (TFP).
To elucidate the structural basis of TFP's inhibition of S100A4 function.

Main Methods:

Crystal structure determination of Ca(2+)-S100A4 bound to TFP.
Nuclear Magnetic Resonance (NMR) chemical shift perturbation studies.
Equilibrium sedimentation and cross-linking assays.
Functional assays assessing TFP's inhibition of S100A4-mediated myosin-IIA filament disassembly.

Main Results:

TFP binds to the hydrophobic pocket of Ca(2+)-S100A4 without inducing significant conformational changes.
TFP binding induces the oligomerization of Ca(2+)-S100A4 into pentameric rings.
Phenothiazine-induced S100A4 oligomerization is responsible for disrupting the S100A4/myosin-IIA interaction.
Significant inhibition of S100A4 function requires TFP concentrations that promote oligomerization.

Conclusions:

TFP inhibits S100A4 function through a unique mechanism involving small molecule-induced oligomerization.
Phenothiazines sequester S100A4, disrupting its interaction with myosin-IIA and inhibiting cancer cell motility.
This study provides a structural and mechanistic basis for developing S100A4-targeting therapeutics.