Substitutions in the β subunits of sickle-cell hemoglobin improve oxidative stability and increase the delay time of sickle-cell fiber formation.

ABSTRACT: After reacting with hydrogen peroxide (H₂O₂), sickle-cell hemoglobin (HbS, βE6V) remains longer in a highly oxidizing ferryl form (HbFe⁴⁺=O) and induces irreversible oxidation of "hot-spot" amino acids, including βCys-93. To control the damaging ferryl heme, here we constructed three HbS variants. The first contained a redox-active Tyr in β subunits (F41Y), a substitution present in Hb Mequon; the second contained the Asp (K82D) found in the β cleft of Hb Providence; and the third had both of these β substitutions. Both the single Tyr-41 and Asp-82 constructs lowered the oxygen affinity of HbS but had little or no effects on autoxidation or heme loss kinetics. In the presence of H₂O₂, both rHbS βF41Y and βF41Y/K82D enhanced ferryl Hb r

SUBMITTER: Meng F 

PROVIDER: S-EPMC6422104 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature