Posttranslational Modification of β141 LEU Associated with the β75(E19)Leu→pro Mutation in HB Atlanta

The recent report of the oxidation of beta 141 Leu in a New Zealand family with Hb Atlanta [ beta 75(E19)Leu--Pro] prompted us to reinvestigate the original Hb Atlanta case from Georgia. Tryptic peptide maps showed that the modified beta CoT-14 peptide was present together with beta AT-14 in isopropanol precipitates of Hb Atlanta. Amino acid analysis confirmed that beta CoT-14 lacked leucine and mass spectrometry indicated that it had an increased mass of 16 Daltons. These findings support the proposition that the beta 75 Leu--Pro substitution in the E helix is the direct cause of the beta 141 Leu oxidation.