The Penultimate Tyrosine Residues are Critical for the Genotoxic Effect of Human Hemoglobin
Oxygen Transport to Tissue XXXIX
Advances in experimental medicine and biology, July 2017
Sandeep Chakane, Vijay Markad, Kisan Kodam, Leif Bülow
Hemoglobin (Hb) is a potent oxidant outside the erythrocyte. The tyrosines α140 and β145 play an important role in the structure and function of Hb by forming switch and hinge contacts. These carboxy-terminal residues of the alpha and beta chains, respectively, were replaced to phenylalanine and several different methods were used to characterize the obtained mutants including a comet and plasmid DNA cleavage assay. It was observed that the genotoxic effect was 40% higher for αY140F compared with the wildtype, the βY145F and the double (αY140/β145F) mutants as determined by the comet assay. Cleavage of purified plasmid DNA after Hb application also revealed that the αY140F mutant showed 2-fold higher activity, while the βY145F and αY140/β145F mutants reduced the activity compared to wildtype Hb. This study clearly indicates that the penultimate tyrosines are involved in the genotoxicity of Hb.
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