Influence of the chemical nature of side chain at beta 108 of hemoglobin A on the modulation of the oxygen affinity by chloride ions. Low oxygen affinity variants of human hemoglobin expressed in transgenic pigs: hemoglobins Presbyterian and Yoshizuka.

Effects of Substitutions of Lysine and Aspartic Acid for Asparagine at β108 and of Tryptophan for Valine at α96 on the Structural and Functional Properties of Human Normal Adult Hemoglobin: Roles of α1β1 and α1β2 Subunit Interfaces in the Cooperative Oxygenation Process

“…These results indicate that the T-states of Hb Yoshizuka and r Hb (RV96W, βN108D) are also more stable than that of Hb A. its ligation state under low temperature and/or in the presence of IHP. This indicates that the molecular basis for the low oxygen affinity of r Hb (RV96W) is that it favors the T conformation as compared to Hb A. r Hb Presbyterian (βN108K) is a low affinity mutant with normal cooperativity (16,17,(37)(38)(39). Ho et al (10) showed that r Hb Presbyterian and r Hb (RV96W, βN108K) also have a similar mechanism for low oxygen affinity and high cooperativity.…”

“…Hb Presbyterian (βN108K) and Hb Yoshizuka (βN108D) are naturally occurring low oxygen affinity mutants ( , ). β108 (G10) is located in the α 1 β 1 subunit interface and in the central cavity of the Hb molecule ().…”

“…Based on the role of the central cavity in modulating the oxygen affinity of Hb, Bonaventura et al (18) proposed that additional cationic groups located in the central cavity of the Hb molecule would destabilize the T quaternary structure by increasing electrostatic repulsion and thereby increase the oxygen affinity. O'Donnell et al (17) have discussed the issue regarding the mechanism of the low oxygen affinity of Hb Presbyterian and Hb Yoshizuka, in light of their own results on these two mutants and the suggestion of Bonaventura et al (18). Their results have prompted us to investigate the electrostatic interactions in the central cavity region of the Hb molecule which cause the equilibrium between the T-and R-states to shift, resulting in different oxygen affinity and cooperativity of the oxygenation process.…”

Probing the Diphosphoglycerate Binding Pocket of HbA and HbPresbyterian (β108Asn → Lys)

“…The mechanism whereby binding of chloride is communicated to the oxygen binding sites at the heme groups has not been determined. However, the influence of the β108 Asn f Lys substitution is muted when the protein is cross-linked at its DPG binding pocket using bis-sulfosuccinimide suberate (7). A comparative mapping of the various functional and structural domains of the mutant protein and an integration of such structural information are critical to establishing the molecular basis of the chloride-induced low oxygen affinity of this protein.…”

“…HbP is currently involved in continuing investigations of hemoglobin-based, acellular oxygen carriers (blood substitutes) (8). In addition, the added positive charge in a key region of the central cavity has made HbP a focus of studies undertaken to better understand both allosteric transitions and the communication pathways between the effector binding site and the oxygen binding sites at the heme moieties (7).…”