Hemoglobin Einstein: Semisynthetic deletion in the B‐helix of the α‐chain

The influence of the deletion of the tetra peptide segment α_23–26 of the B‐helix of the α‐chain of hemoglobin‐A on its assembly, structure, and functional properties has been investigated. The hemoglobin with the deletion, ss‐Hemoglobin‐Einstein, is readily assembled from semisynthetic α_1–141 des_23–26 globin and human β^A‐chain. The deletion of α_23–26 modulates the O₂ affinity of hemoglobin in a buffer/allosteric effector specific fashion, but has little influence on the Bohr effect. The deletion has no influence on the thermodynamic stability of the α₁β₁ and the α₁β₂ interface. The semisynthetic hemoglobin exhibits normal intersubunit interactions at the α₁β₁ and α₁β₂ interfaces as reflected by ¹H‐NMR spectroscopy. Molecular modeling studies of ss‐Hemoglobin‐Einstein suggest that the segment α_28–35 is in a helical conformation, while the segment α_19–22 is the nonhelical AB region. The shortened B‐helix conserves the interactions of α₁β₁ interface. The results demonstrate a high degree of plasticity in the hemoglobin structure that accommodates the deletion of α_23–26 without perturbing its overall global conformation.