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Vanadate inhibits the ATPase activity and DNA binding capability of bacterial MutS. A structural model for the

Roberto J Pezza1, Marcos A Villarreal, Guillermo G Montich

  • 1Centro de Investigaciones en Química Biológica de Córdoba, UNC-CONICET, Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina.

Nucleic Acids Research
|November 1, 2002
PubMed

Insights

Vanadate inhibits the DNA mismatch repair protein MutS by affecting its ATPase activity and DNA binding. This suggests vanadate could modulate the mismatch repair system (MMRS).

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • MutS is a DNA mismatch-binding protein crucial for the DNA post-replicative mismatch repair system (MMRS).
  • The ATPase activity of MutS is essential for its function in DNA repair.

Purpose of the Study:

  • To investigate the effect of vanadate compounds on the function of MutS from Pseudomonas aeruginosa and Escherichia coli.
  • To elucidate the mechanism of vanadate inhibition on MutS ATPase activity and DNA binding.

Main Methods:

  • Biochemical assays to measure ATPase activity.
  • Structural comparison of ATP-binding regions.
  • Molecular docking simulations.
  • Analysis of vanadate's effect on DNA binding, oligomerization, and thermal stability of MutS.

Main Results:

  • Ortho- and decavanadate inhibited the ATPase activity of both P. aeruginosa and E. coli MutS.
  • Structural similarities suggest vanadate inhibits MutS via a mechanism similar to other ABC ATPases.
  • Decavanadate likely inhibits by sterically impeding ATP/ADP exchange.
  • Vanadate also impaired MutS DNA-binding, oligomerization, and thermal stability.

Conclusions:

  • Vanadate acts as an inhibitor of MutS ATPase activity and DNA binding.
  • The findings suggest vanadate could be an intracellular modulator of the MMRS.
  • Understanding vanadate's interaction with MutS provides insights into DNA repair mechanisms.

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