Related Experiment Video

Updated: Jul 9, 2025

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors
10:28

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors

Published on: August 17, 2019

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AAA ATPase protein-protein interactions as therapeutic targets in cancer

Dhiraj Mannar1, Sana Ahmed1, Sriram Subramaniam2

  • 1Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

Current Opinion in Cell Biology
|December 6, 2023
PubMed

Insights

AAA ATPases are crucial enzymes for cell stability. New structural insights from cryo-electron microscopy are advancing the development of targeted cancer therapies by focusing on p97/VCP and RUVBL ATPase inhibitors.

Area of Science:

  • Biochemistry and molecular biology
  • Cellular biology
  • Structural biology

Background:

  • AAA ATPases are essential enzymes regulating cellular homeostasis through protein interactions.
  • Their dysregulation is implicated in cancer, making them potential therapeutic targets.
  • p97/VCP and RUVBL ATPases are key members with emerging inhibitor landscapes.

Purpose of the Study:

  • To review recent advancements in AAA ATPase research.
  • To emphasize the impact of cryo-electron microscopy (cryo-EM) on understanding AAA ATPase structure and function.
  • To highlight the therapeutic potential of targeting AAA ATPases in cancer.

Main Methods:

  • Review of recent scientific literature.
  • Focus on structural biology findings, particularly those derived from cryo-EM.
  • Analysis of inhibitor development for p97/VCP and RUVBL ATPases.

Main Results:

  • Cryo-EM has significantly enhanced the understanding of AAA ATPase structures.
  • Detailed structural information facilitates the design of selective inhibitors.
  • Progress in inhibitor development shows promise for cancer therapy.

Conclusions:

  • Structural insights into AAA ATPases are rapidly advancing.
  • Targeted inhibition of AAA ATPases, like p97/VCP and RUVBL, offers a promising therapeutic strategy for cancers.
  • Cryo-EM is a pivotal technology driving these discoveries.

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