The specify of adenine binding occurs through two hydrogen bonds with the amide backbone of a nearby isoleucine residue. The serine-rich sections suggest potential sites for Mg2+ binding. The Walker B motif is believed to be involved in stabilizing Mg2+-bound water once the metal ion coordinates to an aspartate residue.
In humans, the MMR system is composed of seven proteins that work in a highly synchronized fashion to perform DNA mismatch repair: MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2. These seven proteins form several complexes, including: MutSα, a MSH2•MSH6 heterodimer; MutSβ, a MSH2•MSH3 heterodimer; MutLα, a MLH1•PMS2 heterodimer—and together with the PCNA replication clamp, DNA polymerase δ, and the single-stranded DNA binding protein RPA, the various complexes work synchronously to repair DNA mismatches.20 The structure and function of the first step—recognition of a mismatch but MutS—was discussed (Figure …show more content…
sapiens, M. musculus, and S. cerevisiae provide an overview of the residues and motifs present in MMR, it is sufficient only for inferring the many factors that contribute to disease via MMR mutations. MSH2 is believed to be a facilitator in mismatch repair, stabilizing MSH6 as it recruits other actors in the MMR pathway. Despite the seemingly peripheral role of MSH2, it is known that any major changes to its structure limit its binding to MSH6—and without MSH2, MSH6 does not survive for very long post translation. The downregulation of MSH2 has been implicated in numerous types of cancer, including breast9 and colon2, 18, 22 cancers, endometrial carcinoma, and malignancies of the stomach, small bowel, ovaries, upper uroepithelial tract, biliary tract, skin and brain.X The primary structure of one component of the MutSα dimer, MSH2, has provided insight into the protein and the conclusion that MSH2—and the MMR system in general—is unquestionably