Identification of Hb Zürich [α₂ β₂63(E7)His->arg] by Dna Analysis in a Brazilian Family

Abstract

Hb Zürich, in which the β63(E7) histidine is replaced by arginine, was the first unstable hemoglobin (Hb) variant to be analyzed structurally (1-3). The structural alteration in Hb Zürich leads to particularly interesting functional and clinical consequences. The substitution of arginine for the distal histidine at helix E7 causes a marked change in the space where ligand binding occurs (4). The positively charged arginine attaches to the propionate of the heme, leaving the heme pocket wide open, and allowing ready access to the heme iron. This explains the propensity for individuals with this variant to have hemolytic episodes following ingestion of sulfa derivatives (1,5).