Discovery of a new binding site for the possible gain in neomorphic activity in R132HIDH1

Key Points

• To identify a new binding site associated with neomorphic activity in the R132H_IDH1 variant.
• Characterization of IDH1 catalytic activity in vitro
• Biochemical assays to assess binding affinity
• Structural analysis using X-ray crystallography
• Discovery of a novel binding site that enhances neomorphic activity
• Increased catalytic efficiency observed in the R132H_IDH1 variant
• Potential implications for targeted therapies in related diseases