Distal histidine stabilizes bound O2 and acts as a gate for ligand entry in both subunits of adult human hemoglobin.

ABSTRACT: The role of the distal histidine in regulating ligand binding to adult human hemoglobin (HbA) was re-examined systematically by preparing His(E7) to Gly, Ala, Leu, Gln, Phe, and Trp mutants of both Hb subunits. Rate constants for O(2), CO, and NO binding were measured using rapid mixing and laser photolysis experiments designed to minimize autoxidation of the unstable apolar E7 mutants. Replacing His(E7) with Gly, Ala, Leu, or Phe causes 20-500-fold increases in the rates of O(2) dissociation from either Hb subunit, demonstrating unambiguously that the native His(E7) imidazole side chain forms a strong hydrogen bond with bound O(2) in both the alpha and beta chains (DeltaG(His(E7)H-bond) approximately -8 kJ/mol). As the size of the E7 amino acid is increased from Gly to Phe, decreases in k

SUBMITTER: Birukou I 

PROVIDER: S-EPMC2838306 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature