Regulation of oxygen affinity in hemoglobin variants modeled after bovine hemoglobin

C. Fronticelli, M. Karavitis, W. S. Brinigar

Research output: Contribution to journalArticlepeer-review

Abstract

In human Hb. the mutations β(VlM+H2deleted+T4I+P5A) introduce a low intrinsic oxygen affinity similar to that of bovine Hb. The further introduction of a Lys at β76 β(VlM + H2deleted+T4l +P5A+A76K) introduces into this mutant a modulation of oxygen affinity the Cl- again, similar to bovine Hb [Fronticelli et al.. J. Biol. Chem. 1995]. Except for He at position β4, these amino acid residues are those present in the β-chains of bovine Hb. hi order to investigate whether He at β4 contributes to the decreased oxygen affinity, we have constructed the human Hb mutant β(VlM+H2deleted -f P5A-4-A76) in which βThr4 was nor substituted. In this hemoglobin the mechanism of oxygen affinity modulation by Cl- is still present, but the oxygen affinity is increased. Thus, in bovine Hb, where a Thr is present at β4, the low intrinsic oxygen affinity is not due exclusively to the sequence at the βamino terminal end. In order to test the proposition that in bovine Hb the oxygen linked Cl- binding site is comprised of βLys 8 and βLys 76, we constructed a mutant human hemoglobin β(VlM + H2deleted+T4I+P5A+K8N+A76K) in which βLys 8 was replaced by Asn. This mutant has alow intrinsic oxygen affinity which, however. is not modified by the presence of Cl- in the solution. This result provides further evidence for the presence, in bovine Hb, of an oxygen linked Cl- binding site between the A and E helices of the β-chains.

Original languageEnglish (US)
Pages (from-to)A1424
JournalFASEB Journal
Volume12
Issue number8
StatePublished - Dec 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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