Characterization of a Novel Post-translational Oxidative Modification in the Distal Pocket of a Fetal Hemoglobin (γ -V68M→D) Associated with the Blue Baby Syndrome

摘要

The transition from ferrous to ferric oxidation state via autooxidation was accelerated for the V68M mutant. H_2O_2 byproduct of autooxidation, are involved in the conversion of methionine to aspartic acid in a dose dependent manner. We have also performed labeling experiments using H_2~(18)O_2 to confirm that peroxide is the source of oxygen on the aspartate side chain (see Wayne Hicks, FDA; Wednesday Poster session) Our data links aspartic acid conversion to an autooxidative event involving oxidative side reactions and thus demonstrates how side chain proximity to the reactive heme pocket results in conditions that lead to cyanosis and anemia.