Haemoglobin α2β223Val → Ile produced in Escherichia coli facilitates Hb S polymerization
- 1 April 1990
- journal article
- research article
- Published by Wiley in British Journal of Haematology
- Vol. 74 (4), 531-534
- https://doi.org/10.1111/j.1365-2141.1990.tb06346.x
Abstract
The doubly substituted variant Hb S-Antilles (.beta.6 Glu .fwdarw. Val, .beta.23 Val.fwdarw.Ile) produces sickling in heterozygous carriers. The Csat value for pure deoxyHb S-Antilles is nearly half that of deoxyHb S. Dilute solutions of pure Hb S-Antilles have a lower oxygen affinity than those of Hb A or Hb S. The mutant Hb .alpha.2.beta.223 Val.fwdarw.Ile was synthesized in Escherichia coli. It exhibits a decreased oxygen affinity compared to Hb A and does not polymerize in 1.8 M phosphate buffer. Mixtures of equal amounts of Hb S + Hb .beta.23 Val.fwdarw.Ile have a decreased Csat value compared to mixtures of Hb S+Hb A. The .beta.23 Val in Hb S contributes to the axial contact joining molecules in each single filament. Substituting Ile for Val at this site increases the strength of this contact through hydrophobic interactions, allowing increased stability of the lateral contact between filaments in pair, which is the specific unit structure of polymers in deoxyHb S.Keywords
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