Hemoglobin J Cairo: β 65 (E9) Lys → Gln, a new hemoglobin variant discovered in an Egyptian family

Garel, Marie-Claude; Hassan, W.; Coquelet, M.T.; Goossens, Michel; Rosa, J.; Arous, N.

doi:10.1016/0005-2795(76)90348-2

Cited by 35 publications

(6 citation statements)

References 18 publications

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“…This finding might indicate that the replaced Cys at the ab-C-terminus consumes oxidants produced during incubation and protects the Hb Nb molecule from met-Hb formation. The high oxygen affinity of this variant may also contribute to stabilize the heme Fe(II) ion as observed in Hb Creteil ((#89 Ser -Asn) (41,42 amino acids of aNb-T-14, "0Tyr, and 14'cysteic acid. However, detection of these amino acids on the map was unsuccessful.…”

Section: Saci Discussionmentioning

confidence: 96%

A new hemoglobin variant, hemoglobin Nunobiki [alpha 141 (HC3) Arg----Cys]. Notable influence of the carboxy-terminal cysteine upon various physico-chemical characteristics of hemoglobin.

Shimasaki¹

1985

J. Clin. Invest.

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A new hemoglobin variant, hemoglobin (Hb) Nunobiki, was detected in a Japanese male with marginal erythrocytosis. The Hb Nunobiki component amounted to 13.1% of the total hemoglobin. Structural analysis of this variant established the substitution of a cysteine for an arginine at the carboxy terminus of the a-chain (a]141).The oxygen equilibrium curves of Hb Nunobiki revealed extremely high oxygen affinity with a reduced Hill coefficient n, a decreased alkaline Bohr effect, and a decreased 2,3-diphosphoglyceric acid effect.The isoelectric point of the Hb Nunobiki changed during storage, although the oxyhemoglobin state was maintained. These findings could be accounted for by the specific characteristics of a newly introduced cysteinyl residue.Cysteinyl residue at a141 in Hb Nunobiki did not seem to be involved in the formation of either intermolecular or intramolecular disulfide bonds under physiologic conditions.The low proportion of Hb Nunobiki (13.1%) in the propositus was also discussed after it was verified that he exhibited four a-globin genes per diploid cell.

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Section: Saci Discussionmentioning

confidence: 96%

A new hemoglobin variant, hemoglobin Nunobiki [alpha 141 (HC3) Arg----Cys]. Notable influence of the carboxy-terminal cysteine upon various physico-chemical characteristics of hemoglobin.

Shimasaki¹

1985

J. Clin. Invest.

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“…This residue is located very close to the distal histidine E7, an invariant amino acid site, which is implicated in the oxygenation process (Rohlfs et al 1990). Garel et al (1976) described a human hemoglobin variant in which a glutamine residue—the same found in the dolphin—substitutes the lysine residue in position 65. They found that this new variant results in a moderate decrease in cooperativity without changing the Hb stability.…”

Section: Discussionmentioning

confidence: 99%

Genomic Organization and Differential Signature of Positive Selection in the Alpha and Beta Globin Gene Clusters in Two Cetacean Species

Nery¹,

Opazo²

2013

Genome Biology and Evolution

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The hemoglobin of jawed vertebrates is a heterotetramer protein that contains two α- and two β-chains, which are encoded by members of α- and β-globin gene families. Given the hemoglobin role in mediating an adaptive response to chronic hypoxia, it is likely that this molecule may have experienced a selective pressure during the evolution of cetaceans, which have to deal with hypoxia tolerance during prolonged diving. This selective pressure could have generated a complex history of gene turnover in these clusters and/or changes in protein structure themselves. Accordingly, we aimed to characterize the genomic organization of α- and β-globin gene clusters in two cetacean species and to detect a possible role of positive selection on them using a phylogenetic framework. Maximum likelihood and Bayesian phylogeny reconstructions revealed that both cetacean species had retained a similar complement of putatively functional genes. For the α-globin gene cluster, the killer whale presents a complement of genes composed of HBZ, HBK, and two functional copies of HBA and HBQ genes, whereas the dolphin possesses HBZ, HBK, HBA and HBQ genes, and one HBA pseudogene. For the β-globin gene cluster, both species retained a complement of four genes, two early expressed genes—HBE and HBH—and two adult expressed genes—HBD and HBB. Our natural selection analysis detected two positively selected sites in the HBB gene (56 and 62) and four in HBA (15, 21, 49, 120). Interestingly, only the genes that are expressed during the adulthood showed the signature of positive selection.

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“…Since the determination of the amino acid sequence of human hemoglobin in 1961, 20 numerous variants of human hemoglobin with exchanges of different amino acid residues have been identified. [21][22][23][24][25] Those modifications in amino acid sequences can cause altered oxygen affinities, [26][27][28][29][30] and the analysis of these variants after tryptic digestion gives rise to peptides with different molecular weight, sequence, or both compared to normal human Hb. In addition, posttranslational modifications of hemoglobin, i.e., nonenzymatic glycosylation, are monitored frequently in case of metabolic disorders such as diabetes, resulting in modifications of the N-termini of hemoglobin R-and β-chains as well as different lysine residues.…”

Section: Resultsmentioning

confidence: 99%

Doping Control Analysis of Bovine Hemoglobin-Based Oxygen Therapeutics in Human Plasma by LC−Electrospray Ionization-MS/MS

Thevis

Loo

et al. 2003

Anal. Chem.

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Since January 2000, hemoglobin-based oxygen carriers, such as Hemopure, belong to the list of prohibited substances of the International Olympic Committee. Hemopure is based on bovine hemoglobin, which is intra- and intermolecularly cross-linked by glutaraldehyde units causing an average molecular weight of ∼250 000. Bovine and human hemoglobins differ by 15% in amino acid sequence; hence, tryptic digestion of these proteins generates species-common and -unique peptides. Those specific fragments originate from the α- and β-subunits of hemoglobin, such as bovine Hb peptides α69 - 90 (2367.2 Da) or β40 - 58 (2089.9 Da). By means of LC−MS/MS, peptides of human and bovine hemoglobin can be separated and identified, enabling the determination of compounds based on Hb of bovine origin and thus the administration of oxygen carriers such as Hemopure. Blank plasma samples were spiked with Hemopure or human or bovine hemoglobin, filtered, enzymatically digested, and analyzed on an Agilent 1100 Series HPLC interfaced to an Applied Biosystems API 2000 triple quadrupole mass spectrometer. In plasma aliquots of 50 μL containing 50 μg of Hemopure (1 mg/mL), peptides of bovine hemoglobin were confirmed, and blank plasma samples as well as 68 specimens of high-performance athletes were tested with the developed procedure.

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Hemoglobin J Cairo: β 65 (E9) Lys → Gln, a new hemoglobin variant discovered in an Egyptian family

Cited by 35 publications

References 18 publications

A new hemoglobin variant, hemoglobin Nunobiki [alpha 141 (HC3) Arg----Cys]. Notable influence of the carboxy-terminal cysteine upon various physico-chemical characteristics of hemoglobin.

A new hemoglobin variant, hemoglobin Nunobiki [alpha 141 (HC3) Arg----Cys]. Notable influence of the carboxy-terminal cysteine upon various physico-chemical characteristics of hemoglobin.

Genomic Organization and Differential Signature of Positive Selection in the Alpha and Beta Globin Gene Clusters in Two Cetacean Species

Doping Control Analysis of Bovine Hemoglobin-Based Oxygen Therapeutics in Human Plasma by LC−Electrospray Ionization-MS/MS

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