Molecular Pathology of Human Haemoglobin

Intermediate structure of normal human haemoglobin: Methaemoglobin in the deoxy quaternary conformation

“…The addition of acrylamide to the standard human deoxy-haemoglobin crystallization mixture of Perutz (1968) yields no crystals, since the protein's solubility is greatly increased. Therefore the following modification of the usual recipe was used (contents of the best vial from a range of salt concentrations are described) : 1-O ml saturated ammonium sulphate, 0.6 ml distilled water, 4.2 ml solution C and 0.1 ml acrylamide solution I, to which is added (under pure N,) 0.7 ml human oxy-haemoglobin (6%) and 0.1 ml ferrous citrate.…”

“…Therefore the following modification of the usual recipe was used (contents of the best vial from a range of salt concentrations are described) : 1-O ml saturated ammonium sulphate, 0.6 ml distilled water, 4.2 ml solution C and 0.1 ml acrylamide solution I, to which is added (under pure N,) 0.7 ml human oxy-haemoglobin (6%) and 0.1 ml ferrous citrate. All solutions are as normally used (Perutz, 1968; solution C is made of 0.8 vol. Deoxy crystals prepared in the above manner were rather tightly stuck to the sides of their vials and had to be broken off; this seldom damaged the removed portion, but did produce small conchoid surface fractures as in chipped glass.…”

A new haemoglobin J from Turkey ‐ HB Ankara (β 10 (A7) Ala → Asp).

“…Asparagine also appears as aspartic acid on amino acid analysis after acid hydrolysis, but an alanine to asparagine substitution, which in any case could not arise from a single point mutation, could be eliminated 122 on the basis of the electrophoretic mobility of both the variant haemoglobin and peptide. Dansyl-Edman degradation of the peptide/3JTplI showed that alanine /310 had been replaced by aspartic acid, making it clear Generally speaking, substitution of amino acids at sites which are external in the haemoglobin quaternary structure do not grossly affect the properties of the tetramer [11 ]. The substitution in Hb Ankara is at an external site, which therefore plays no part in subunit contacts or haem binding; in view of the fact that the relative proportion of the variant haemoglobin was approximately that for a normal, stable/~-chain variant, it seems unlikely that the presence of Hb Ankara in the erythrocytes of this patient would have contributed to her anaemia.…”

Functional properties of hemoglobin Rainier

“…This is particularly fruitful possible to correlate findings on the functional molecule with the structural information analysis of the tridimensional structure [2] .…”