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Article Dans Une Revue Journal of Biological Chemistry Année : 1997

Influence of the A Helix Structure on the Polymerization of Hemoglobin S

Véronique Baudin
  • Fonction : Auteur
Jean Kister
  • Fonction : Auteur
Claude Poyart
  • Fonction : Auteur
Josée Pagnier
  • Fonction : Auteur

Résumé

Hb S variants containing Lys-␤132 3 Ala or Asn substitutions were engineered to evaluate the consequences of the A helix destabilization in the polymerization process. Previous studies suggested that the loss of the Glu-␤7-Lys-␤132 salt bridge in the recombinant Hb ␤E6V/E7A could be responsible for the destabilization of the A helix. The recombinant Hb (rHb) S/␤132 variants polymerized with an increased delay time as well as decreased maximum absorbance and Hb solubility values similar to that of Hb S. These data indicate that the strength of the donor-acceptor site interaction may be reduced due to an altered conformation of the A helix. The question arises whether this alteration leads to a true inhibition of the polymerization process or to qualitatively different polymers. The oxygen affinity of the ␤132 mutated rHbs was similar to that of Hb A and S, whereas the cooperativity and effects of organic phosphates were reduced. This could be attributed to modifications in the central cavity due to loss of the positively charged lysine. Since Lys-␤132 is involved in the stabilization of the ␣1-␤1 interface, the loss of the ␤132(H10)-␤128(H6) salt bridge may be responsible for the marked thermal instability of the ␤132 mutated rHbs.
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Dates et versions

hal-03681429 , version 1 (30-05-2022)

Identifiants

Citer

Sophie Lesecq, Véronique Baudin, Jean Kister, Claude Poyart, Josée Pagnier. Influence of the A Helix Structure on the Polymerization of Hemoglobin S. Journal of Biological Chemistry, 1997, 272 (24), pp.15242-15246. ⟨10.1074/jbc.272.24.15242⟩. ⟨hal-03681429⟩
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