Influence of the A helix structure on the polymerization of hemoglobin S.

The Journal of Biological Chemistry
S LesecqJ Pagnier

Abstract

Hb S variants containing Lys-beta132 --> 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-beta7-Lys-beta132 salt bridge in the recombinant Hb betaE6V/E7A could be responsible for the destabilization of the A helix. The recombinant Hb (rHb) S/beta132 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 beta132 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-beta132 is involved in the stabilization of the alpha1-beta1 interface, the loss of the beta132(H10)-beta128(H6) salt bridge may be responsible for the marked therma...Continue Reading

References

Jan 1, 1978·Hemoglobin·J S SackW E Love
Jan 1, 1992·Protein Science : a Publication of the Protein Society·M T BihoreauC Poyart
Mar 1, 1989·British Journal of Haematology·J V LangdownR W Carrell
Jan 20, 1988·Journal of Molecular Biology·B CarragherR Josephs
Mar 8, 1988·Biochemistry·M C MardenC Poyart
Dec 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·N MonplaisirJ Rosa
Sep 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·D W RodgersS J Edelstein
Nov 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·K NagaiC Poyart
Sep 14, 1971·Journal of Molecular Biology·R M Bookchin, R L Nagel
May 15, 1984·Journal of Molecular Biology·G FermiR Fourme
Aug 25, 1981·Journal of Molecular Biology·S J Edelstein
Feb 28, 1980·Nature·R L NagelO Castro

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Citations

Jul 9, 2003·British Journal of Haematology·Christophe FabletRhoda Elison Hirsch

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