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Haemoglobin α 2 β 2 23Val → Ile produced in Escherichia coli facilitates Hb S polymerization
Author(s) -
Pagnier J.,
BaudinChich V.,
Lacaze N.,
Bohn B.,
Poyart C.
Publication year - 1990
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1990.tb06346.x
Subject(s) - polymerization , protein filament , crystallography , polymer , chemistry , escherichia coli , oxygen , mutant , stereochemistry , biochemistry , organic chemistry , gene
Summary The doubly substituted variant Hb S‐Antilles (β6 Glu → Val, β3 Val → Ile) produces sickling in heterozygous carriers. The C sat 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 α 2 β 2 23 Val → Ile was synthesized in E. 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 β23 Val → Ile have a decreased C sat value compared to mixtures of Hb S + Hb A. The β23 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.