Prominent species in the MutS ATPase pathway and their interactions with DNA. According to the kinetic parameters measured for MutS ATPase, in the absence of DNA or in the presence of fully matched DNA, the first slow, rate-limiting step occurs after ATP hydrolysis at S1, indicating that S1ADP–S2ATP might be a stable species in this pathway. In contrast, when MutS is bound to a DNA mismatch, the first rate-limiting step occurs prior to ATP hydrolysis at S1, indicating that S1ATP–S2ATP and perhaps S1ATP–S2ADP as well might be the stable species in this ATPase pathway. The model also depicts possible interactions between various nucleotide-bound MutS species and mismatched DNA based on results from DNA-binding experiments in this study and in the literature. Dashed arrows indicate steps that may not happen in immediate succession.