Histidine and Proline are Important Sites of Free Radical Damage to Proteins

Our hypothesis that proline and histidine are major sites of damage during radical attack upon proteins, becoming respectively glutamate and aspartate. was investigated using proteins biosynthetically labelled with radioactive proline or histidine as targets. Free radicals were generated by copper and H₂O₂, or by gamma radiolysis. Protein-bound histidine was substantially converted into aspartate. Much proline was modified during radical attack, but it was not converted into glutamate. We conclude that histidine and proline are important sites of protein attack by radicals; protein cleavage may result from these reactions.