Hemoglobin St Luke's or α^95Arg₂ (G2) β₂

Abstract

A new hernoglobin variant, designated hemoglobin-St Luke's, was detected by routine starch-gel electrophoresis in four members of a Maltese family. The carriers of this abnormality are clinically and hematologically normal. Structural analyses showed the replacement of prolyl residue in position 95 (G2) of the alpha chain by an arginyl residue. The relative amount of hemoglobin-St Luke's present in the red cell hemolysates of its carrier is approximately loo/,, compared to about 2301, for hemoglobin-G Georgia and 15Oj, for hemoglobin-Rampa (the other two variant,s in which prolyl residue a95 (G2) is replaced). Sedimentation velocity studies of hemoglobin-St Luke's in NaCl solutions of increasing concentration up to 2 M indicak &hat the oxy derivative is extensively dissociated into dimers in 0.1 M NaCl a t neutral pH; whereas under the same conditions, the deoxygenated molecule retains a tetrameric structure. In the deoxy state, appreciable tetramer formation occurs even in 2 M NaCI. In addition, association-dissociation in oxyor cyanferrihemoglobin St Luke's is both pH and temperature dependent.Hemoglobins G Georgia and Rainpa are variants in which the proIyl residue in position 95 of the cx chain is replaced by a leucyl and a seryl residue, respectively [I, 2 ) . The liganded derivatives of these abnormal hemoglobins are extensively dissociated into dimers in NaCl solutions of low molarity and a t neutral pH [3]. I n contrast, the deoxygenated derivatives of the two variants are tetramers under the same conditions. The substitution of the prolyl residue occurs a t a site which involves one of the critical contacts ; these contacts are broken when hemoglobin tetramers dissociate into dimers [41. The introduction of either a leucyl residue or a seryl residue in position a95 (G2) ruptures the contacts normally present between Pro-ag5 (G2) and Trp-/337 (C3) in oxygenated hemoglobin [4], and causes an extensive disruption of the al-& contact, probably because the contact becomes accessible to water 131. The greatly increased degree of dimer formation of the two variants is associated with an increased affinity for oxygen and a decrease in heme-heme interaction [3] ; carriers of these abnormalities appear normal.Abbreviation. Hb, hemoglobin.We recently observed an additional variant in which the prolyl residue in position a95 is substituted by an arginyl residue. The variant, t-ermed HbSt Luke's, was present in four members of a Maltese family. This paper describes results of structural analyses and data from sedimentation velocity analyses of the oxy (or cyanferri) and deoxy forms of Hb-St Luke's as a function of salt concentration, pH, and temperature. Results of a few oxygen equilibrium experiments are also included. MATERIALS AND METHODSBlood samples from members of family M were collected with EDTA as anticoagulant. Hematological studies were made by standard methods [5]. Parts of the samples were mailed by air from Malta to Augusta (Georgia, U.S.A.). Hemolysates were prepared by mixing 1 vol. washed packed cel...

Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program

“…According to the literature, Hb Hasharon would not cause clinical or hematological abnormalities unless co-inherited with alpha thalassemia (19, 20) as reported by other Brazilian studies (18, 19, 21, 22) . Patients with Hb Ottawa and Hb St. Luke's were considered normal upon clinical and hematological evaluation (8, 23, 24) . The mutation for Hb Etobicoke occurs at codon 84 (F5) of the HBA gene (Ser>Arg).…”

The linkage of Hb Valletta [?2?287(F3)Thr?Pro] and Hb F-Malta-I [?2 G?2117(G19)His?Arg] in the Maltese population

“…They can also be found in the many Maltese who emigrated primarily to Australia, Canada, and the United States. One variant is the high oxygen affinity chain abnormality Hb St. Luke's or a295 (G2)Pro-->Arg 132 (Bannister et al 1972); another is the Gy chain variant Hb F-Malta-I or ct2Gy2117(G19) His-->Arg (Cauchi et al 1969), which is found in about 1% of all newborn babies; Hb Camperdown or ct2132104(G6) Arg--~ Ser (Wilkinson et al 1975), and Hb Long Island-…”

Development of biochemistry and molecular biology in Malta

“…Hemoglobin F‐Malta had been discovered in 1969 by Maurice Cauchi working in the clinical pathology laboratory of St. Luke's Hospital (1). The human hemoglobin work was encouraged and sustained by Joe L. Grech (a senior consultant in Clinical Biochemistry at St Luke Hospital) and resulted in the discovery of Hemoglobin St. Luke's (2) and a working visit by T.H.J. Huisman of the Medical College of Georgia, Augusta, USA.…”