A new β-chain haemoglobin variant with increased oxygen affinity: Hb Roma [β115(g17)Ala → Val]

Background

Haemoglobin Roma [β115(G17)Ala → Val] is a new adult haemoglobin variant found in a patient presenting a mild hypochromia and microcytosis. We studied this previously uncharacterised variant in order to evaluate the effect on the structural and funcional properties of the Ala → Val substitution at the α1β1 interface.

Methods and results

The variant chain was identified by direct DNA sequencing of the β-globin gene, which revealed a GCC → GTC mutation in codon 115. This mutation was confirmed by mass spectrometric analysis of the tetramers and peptides. The oxygen-binding properties of the haemoglobin A/haemoglobin Roma mixture, in which the variant makes up 25% of the haemoglobins, showed a significant increase in oxygen affinity with respect to normal haemoglobin A, both in the absence and presence of 2,3-bisphosphoglycerate. The role of the βG17 position, situated at the α₁β₁ interface, has been examined using computational models of haemoglobin Roma and other known βG17 variants, in comparison with normal haemoglobin A.

Conclusions

This study suggests that the β115(G17)Ala → Val substitution at the α1β1 interface is responsible for increased oxygen affinity and mild destabilisation of the haemoglobin Roma.

General significance

An amino acid substitution at the G17 position of the α1β1 interface may result in stabilisation of the high affinity R-state of the haemoglobin molecule.     

Hb Riesa or β93 (F9) Cys→Ser, a new electrophoretically silent haemoglobin variant interfering with haemoglobin A1c measurement

A new β variant was found in a German diabetic patient whose blood samples appeared to contain 45% Hb A(1c) using Bio-Rad Variant V-II A1c-analyzer but 7.6% on boronate affinity chromatography. Structural studies using, HPLC, mass spectrometry, and the genomic DNA analysis revealed a new substitution in which the cysteine residue at position β93 was replaced by serine. The variant was named Hb Riesa or β93 (F9) Cys→Ser and accounted for 54.3% of the total haemoglobin. This suggests that the protein-synthesis processes for the mutant could be slightly more promoted than those of the wild-type. Hb Riesa is clinically and electrophoretically silent.     

Spin crossover behavior of a one-dimensional polymeric-chain compound {[Fe(abpt)2(μ-Ni(CN)4)]·xH2O}n (x = 0.5 → 0): Synthesis, spectral, thermal and magnetic properties

A one-dimensional polymeric-chain iron(II)-nickel(II) cyanido-bridged complex of the composition {[Fe(abpt)₂(μ-Ni(CN)₄)]·0.5H₂O}_n (1·0.5H₂O), where abpt = 4-amino-3,5-di-2-pyridyl-4H-1,2,4-triazole, was prepared and characterized by elemental and thermal analyses, FTIR and ⁵⁷Fe Mössbauer spectroscopies, and magnetic measurements. The incomplete spin crossover phenomenon was observed with approximately 12% of the frozen high-spin fraction at low temperatures and with the spin transition critical temperature above room temperature.     

On the solvatochromic properties of the oxalate-bridged complexes [(BuCO2)3M2]2(μ-O2C2O2) where M = Mo or W

The room temperature electronic absorption spectra of the oxalate bridged MM quadruply bonded complexes [(^tBuCO₂)₃M₂]₂(μ-O₂C₂O₂), where M = Mo or W have been recorded in H₂O, THF:H₂O mixtures, THF, CH₂Cl₂, toluene, DMSO, aniline, toluene saturated with N,N-dimethylaniline and ethanol. The strong absorptions in the visible region of the electronic absorption spectra assignable to the metal-to-ligand (bridge) charge transfer are shown to be highly solvent dependent. Those samples prepared in H₂O, CH₂Cl₂ and toluene are shown to comprise of a suspension of microcrystalline particles ranging in size from 100 nm to 5 μm. Individual particles were found by scanning electron microscopy to have an aspect ratio of ∼10:1, all being needle shaped. The spectra in THF, EtOH, aniline, DMSO and toluene-N,N-dimethylaniline all show similar vibronic progressions and are attributed to discrete solvated molecular species. The spectra recorded in aniline are notably red-shifted which is proposed to arise from a combination of hydrogen bonding and Lewis base stabilization of the photoexcited state.