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

Abstract

The recent report of the oxidation of β141 Leu in a New Zealand family with Hb Atlanta [β75(E19)Leu→Pro] prompted us to reinvestigate the original Hb Atlanta case from Georgia. Tryptic peptide maps showed that the modified β^COT-14 peptide was present together with β^AT-14 in isopropanol precipitates of Hb Atlanta. Amino acid analysis confirmed that βCOT-14 lacked leucine and mass spectrometry indicated that it had an increased mass of 16 Dal tons. These findings support the proposition that the β75 Leu→Pro substitution in the E helix is the direct cause of the β141 Leu oxidation.