PMID:12409461
| Citation |
Pezza, RJ, Villarreal, MA, Montich, GG and Argaraña, CE (2002) 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. Nucleic Acids Res. 30:4700-8 |
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| 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 DNA-binding 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. |
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| Keywords |
Adenosine Diphosphate/metabolism; Adenosine Triphosphatases/antagonists & inhibitors; Adenosine Triphosphatases/chemistry; Adenosine Triphosphatases/metabolism; Adenosine Triphosphate/metabolism; Amino Acid Motifs; Amino Acid Sequence; Bacterial Proteins; DNA/genetics; DNA/metabolism; DNA-Binding Proteins/antagonists & inhibitors; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/metabolism; Electrophoretic Mobility Shift Assay; Escherichia coli/enzymology; Escherichia coli Proteins/antagonists & inhibitors; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/metabolism; Ligands; Models, Molecular; Molecular Sequence Data; MutS DNA Mismatch-Binding Protein; Oligodeoxyribonucleotides/chemistry; Oligodeoxyribonucleotides/genetics; Oligodeoxyribonucleotides/metabolism; Protein Conformation; Pseudomonas aeruginosa/enzymology; Scattering, Radiation; Temperature; Vanadates/chemistry; Vanadates/metabolism; Vanadates/pharmacology |
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