Allosteric modulation by tertiary structure in mammalian hemoglobins: Introduction of the functional characteristics of bovine hemoglobin into human hemoglobin by five amino acid substitutions

Clara Fronticelli, Maria Teresa Sanna, Gabriela C. Perez-Alvarado, Michael Karavitis, A. Lien Lu, William S. Brinigar

Research output: Contribution to journalArticlepeer-review

Abstract

Bovine erythrocytes do not contain 2,3-diphosphoglycerate, the principal allosteric effector of human hemoglobin. Bovine hemoglobin has a lower oxygen affinity than human hemoglobin and is regulated by physiological concentrations of chloride (Fronticelli, C., Bucci, E., and Razynska, A. (1988) J. Mol. Biol. 202, 343-348). It has been proposed that the chloride regulation in bovine hemoglobin is introduced by particular amino acid residues located in the amino-terminal region of the A helix and in the E helix of the β subunits (Fronticelli, C. (1990) Biophys. Chem. 37, 141-146). In accordance with this proposal we have constructed two mutant human hemoglobins, β(V1M+H2deleted+T4I+P5A) and β(V1M+H2deleted+T4I+P5A+A76K). These are the residues present at the proposed locations in bovine hemoglobin except for isoleucine at position 4. Oxygen binding studies demonstrate that these mutations have introduced into human hemoglobin the low oxygen affinity and chloride sensitivity of bovine hemoglobin and reveal the presence of a previously unrecognized allosteric mechanism of oxygen affinity regulation where all the interactions responsible for the lowered affinity and chloride binding appear to be confined to individual β subunits.

Original languageEnglish (US)
Pages (from-to)30588-30592
Number of pages5
JournalJournal of Biological Chemistry
Volume270
Issue number51
DOIs
StatePublished - Dec 22 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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