Adult and fetal haemoglobin J-Sardegna [alpha50(CE8)His-->Asp]: functional and molecular modelling studies

Biochem J. 2000 Feb 15;346 Pt 1(Pt 1):193-9.

Abstract

Haemoglobin (Hb) J-Sardegna [alpha50(CE8)His-->Asp] is a haemoglobin variant characteristic of subjects from the island of Sardinia. Here we report a study of the functional properties of both fetal and adult Hb J-Sardegna. The results indicate that adult Hb J-Sardegna displays an oxygen affinity that is higher than that of adult Hb only in the presence of 2,3-diphosphoglycerate (2,3-DPG). On the contrary, at 20 degrees C, the oxygen affinity of fetal Hb J-Sardegna is identical to that of normal fetal haemoglobin, both in the presence and in the absence of 2,3-DPG. A significant difference between these two systems (i.e. a higher oxygen affinity of fetal Hb J-Sardegna) shows up very clearly only when temperature is increased to 37 degrees C. Hence in fetal Hb, the main effect of the amino acid substitution is a decrease in the overall enthalpy change of oxygenation. The results outline the role of the alpha(1)-beta(1) interface in assessing the thermodynamics of oxygen binding. The functional properties of both adult and fetal Hb J-Sardegna have been interpreted at the structural level in light of the results obtained by a computational modelling approach performed in comparison with HbA and Hb Aichi, a variant characterized by a different mutation [alpha50(CE8)His-->Arg] at the same position.

Publication types

  • Comparative Study

MeSH terms

  • 2,3-Diphosphoglycerate / metabolism
  • Adult
  • Aging / blood*
  • Amino Acid Substitution / genetics*
  • Arginine / genetics
  • Aspartic Acid / genetics
  • Binding Sites
  • Computer Simulation
  • Crystallography, X-Ray
  • Fetal Blood / chemistry*
  • Genetic Variation / genetics
  • Hemoglobin J / chemistry*
  • Hemoglobin J / genetics
  • Hemoglobin J / metabolism*
  • Hemoglobins, Abnormal / chemistry
  • Hemoglobins, Abnormal / genetics
  • Hemoglobins, Abnormal / metabolism
  • Histidine / genetics
  • Humans
  • Hydrogen-Ion Concentration
  • Infant, Newborn
  • Models, Molecular*
  • Oxygen / metabolism
  • Temperature
  • Thermodynamics
  • Time Factors

Substances

  • Hemoglobins, Abnormal
  • Hemoglobin J Sardegna
  • 2,3-Diphosphoglycerate
  • Aspartic Acid
  • Histidine
  • Hemoglobin J
  • hemoglobin Aichi
  • Arginine
  • Oxygen