title: Adult and fetal haemoglobin J-Sardegna [alpha50(CE8)His-->Asp]: functional and molecular modelling studies.
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.
authors.affiliation: Department of Biochemistry and Human Physiology, University of Cagliari, 09042 Monserrato Cagliari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Corda
authors.forename: M C
authors.initials: MC
authors.lastname: De Rosa
authors.forename: M G
authors.initials: MG
authors.lastname: Pellegrini
authors.forename: M T
authors.initials: MT
authors.lastname: Sanna
authors.forename: A
authors.initials: A
authors.lastname: Olianas
authors.forename: A
authors.initials: A
authors.lastname: Fais
authors.forename: L
authors.initials: L
authors.lastname: Manca
authors.forename: B
authors.initials: B
authors.lastname: Masala
authors.forename: B
authors.initials: B
authors.lastname: Zappacosta
authors.forename: S
authors.initials: S
authors.lastname: Ficarra
authors.forename: M
authors.initials: M
authors.lastname: Castagnola
authors.forename: B
authors.initials: B
authors.lastname: Giardina
mesh_terms: D019794:2,3-Diphosphoglycerate / Q000378:metabolism; D000328:Adult; D000375:Aging / Q000097:blood*; D019943:Amino Acid Substitution / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D005312:Fetal Blood / Q000737:chemistry*; D014644:Genetic Variation / Q000235:genetics; D006448:Hemoglobin J / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006639:Histidine / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007231:Infant, Newborn; D008958:Models, Molecular; D010100:Oxygen / Q000378:metabolism; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D006455:Hemoglobins, Abnormal; C043667:Hemoglobin J Sardegna; D019794:2,3-Diphosphoglycerate; D001224:Aspartic Acid; D006639:Histidine; D006448:Hemoglobin J; C041175:hemoglobin Aichi; D001120:Arginine; D010100:Oxygen