Functional alterations in adult and fetal hemoglobin Sassari Asp-alpha 126(H9)-->His. The role of alpha 1 alpha 2 contact.
The effects of pH, organic phosphates (2,3-diphosphoglycerate), and temperature on the functional properties of both adult and fetal hemoglobin Sassari alpha (Asp-126-->His) have been studied. The functional properties of the adult variant are characterized by the following: (i) an oxygen affinity higher than that of normal HbA in all the experimental conditions used; (ii) a dramatic reduction of homotropic interactions (n50 very close to unity); and (iii) a significant decrease of the effect of 2,3-diphosphoglycerate, which is 35% lower than that observed on HbA. The fetal variant shows an increased oxygen affinity compared with normal HbF and an almost abolished heme-heme interaction. The molecular basis of these functional differences is discussed in terms of the possible role played by the substitution of alpha (Asp-26-->His) on the stability of the R state of the molecule due to a decreased interaction at the level of alpha 1 alpha 2 contact.
Sanna
M T
MT
Institute of Biological Chemistry, University of Cagliari, Italy.
Giardina
B
B
Scatena
R
R
Pellegrini
M
M
Olianas
A
A
Manca
L
L
Masala
B
B
Castagnola
M
M
Corda
M
M
D000328:Adult; D000595:Amino Acid Sequence; D001224:Aspartic Acid; D005260:Female; D005312:Fetal Blood; D005319:Fetal Hemoglobin / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D006580:Genetic Carrier Screening; D006441:Hemoglobin A / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D006455:Hemoglobins, Abnormal / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D006639:Histidine; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007231:Infant, Newborn; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D010108:Oxyhemoglobins / Q000378:metabolism; D017354:Point Mutation
D006455:Hemoglobins, Abnormal; D046911:Macromolecular Substances; D010108:Oxyhemoglobins; C053966:hemoglobin Sassari; D001224:Aspartic Acid; D006639:Histidine; D006441:Hemoglobin A; D005319:Fetal Hemoglobin