title: The role of proline beta 5(A2) in the functional properties of human adult hemoglobin.
abstract: The replacement of beta 5(A2)Pro by Arg in Hb Warwickshire appears to be without an effect on the functional properties of human Hb A, despite adding two external positive charges close to the central cavity of the hemoglobin tetramer, along the dyad axis. To clarify the role of this portion of the molecule involved in oxygen-linked anion binding, we have engineered the recombinant hemoglobin alpha 2 beta (2)5(A2)Pro-->Ala[rHb beta 5(A2)Pro-->Ala]. The rHb beta 5(A2)Pro-->Ala exhibits an increased oxygen affinity compared to Hb A, with normal heterotropic effects in standard conditions. The increased oxygen affinity may be attributed to the absence of proline, which would render the A helix more flexible, thus destabilizing the T structure. The normal functional properties of Hb Warwickshire may be due to the regulation of oxygen affinity by electrostatic effects involving diffusible anions not bound to any specific site.
authors: INSERM U299, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
authors: V
authors: V
authors: Baudin
authors: J
authors: J
authors: Kister
authors: G
authors: G
authors: Caron
authors: V
authors: V
authors: Jonval
authors: C
authors: C
authors: Poyart
authors: J
authors: J
authors: Pagnier
mesh_terms: D019794:2,3-Diphosphoglycerate; D000328:Adult; D001120:Arginine / Q000737:chemistry*; D001665:Binding Sites; D004163:Diphosphoglyceric Acids / Q000737:chemistry; D006441:Hemoglobin A / Q000737:chemistry / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D011392:Proline / Q000737:chemistry*; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D004163:Diphosphoglyceric Acids; D006455:Hemoglobins, Abnormal; D011994:Recombinant Proteins; D019794:2,3-Diphosphoglycerate; D006441:Hemoglobin A; C043183:hemoglobin Warwickshire; D001120:Arginine; D011392:Proline