Vanadate inhibits the ATPase activity and DNA binding capability of bacterial MutS. A structural model for the vanadate-MutS interaction at the Walker A motif

TLDR: It is proposed that the orthovanadate inhibition of MutS ATPase can take place by a similar mechanism to that described for other ATPases, and considering that vanadate is an intracellular trace component, this compound could be considered as a new modulator of the MMRS.

Abstract: MutS, a member of the ABC ATPases superfamily, is a mismatch DNA-binding protein constituent of the DNA post-replicative mismatch repair system (MMRS). In this work, it is shown that the ATPase activity of Pseudomonas aeruginosa and Escherichia coli MutS is inhibited by ortho- and decavanadate. Structural comparison of the region involved in the ATP binding of E.coli MutS with the corresponding region of other ABC ATPases inhibited by vanadate, including the myosin‐ orthovanadate‐Mg complex, showed that they are highly similar. From these results it is proposed that the orthovanadate inhibition of MutS ATPase can take place by a similar mechanism to that described for other ATPases. Docking of decavanadate on the ATP-binding region of MutS showed that the energetically more favorable interaction of this compound would take place with the complex MutS‐ ADP‐Mg, suggesting that the inhibitory effect could be produced by a steric impediment of the protein ATP/ADP exchange. Besides the effect observed on the ATPase activity, vanadate also affects the DNAbinding capability of the protein, and partially inhibits the oligomerization of MutS and the temperature-induced inactivation of the protein. From the results obtained, and considering that vanadate is an intracellular trace component, this compound could be considered as a new modulator of the MMRS.