Allosteric effects of chloride ions at the intradimeric α1β1 and α2β2 interfaces of human hemoglobin

Rujan, Iulian; Russu, Irina M.

doi:10.1002/prot.10240

Cited by 6 publications

(3 citation statements)

References 40 publications

(49 reference statements)

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“…Nevertheless, the NMR data showed substantially better agreement with PDB 1IRD than the oxyHbA model by Shaanan, demonstrating that high resolution X-ray data are important when comparing data from the two biophysical techniques. This is further shown by NMR experiments on deoxyHbA, 48 which gave better agreement with PDB 1A3N 22 than 2HHB due to the rotamer error in the latter model at His103α. The use of 1HHO and 2HHB as ''canonical'' models against which others are compared is therefore clearly a dangerous practice prone to give spurious differences.…”

Section: Discussionmentioning

confidence: 66%

1.25 Å Resolution Crystal Structures of Human Haemoglobin in the Oxy, Deoxy and Carbonmonoxy Forms

Park

Yokoyama

Shibayama

et al. 2006

Journal of Molecular Biology

282

350

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Section: Discussionmentioning

confidence: 66%

1.25 Å Resolution Crystal Structures of Human Haemoglobin in the Oxy, Deoxy and Carbonmonoxy Forms

Park

Yokoyama

Shibayama

et al. 2006

Journal of Molecular Biology

282

350

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“…Several studies of human hemoglobin mutations have documented that even small changes in these packing contacts may affect hemoglobin stability and oxygen binding affinity [ 13 - 16 ]. Further, allosteric effects of chloride ions at the intradimer interfaces cause significant changes in the rates of proton exchange upon ligand binding [ 17 ]. Intriguingly, the Leu55β(D6)- > Ser and Pro119α(H2)- > Ala replacements at the α1β1 interface in the bar-headed ( Anser indicus ) and Andean geese ( Chloephaga melanoptera ), respectively, were found to increase the hemoglobin oxygen affinity in these high-altitude species by the elimination of intersubunit contacts [ 18 - 21 ].…”

Section: Introductionmentioning

confidence: 99%

The conserved Phe GH5 of importance for hemoglobin intersubunit contact is mutated in gadoid fish

et al. 2014

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BackgroundFunctionality of the tetrameric hemoglobin molecule seems to be determined by a few amino acids located in key positions. Oxygen binding encompasses structural changes at the interfaces between the α1β2 and α2β1 dimers, but also subunit interactions are important for the oxygen binding affinity and stability. The latter packing contacts include the conserved Arg B12 interacting with Phe GH5, which is replaced by Leu and Tyr in the αA and αD chains, respectively, of birds and reptiles.ResultsSearching all known hemoglobins from a variety of gnathostome species (jawed vertebrates) revealed the almost invariant Arg B12 coded by the AGG triplet positioned at an exon-intron boundary. Rare substitutions of Arg B12 in the gnathostome β globins were found in pig, tree shrew and scaled reptiles. Phe GH5 is also highly conserved in the β globins, except for the Leu replacement in the β1 globin of five marine gadoid species, gilthead seabream and the Comoran coelacanth, while Cys and Ile were found in burbot and yellow croaker, respectively. Atlantic cod β1 globin showed a Leu/Met polymorphism at position GH5 dominated by the Met variant in northwest-Atlantic populations that was rarely found in northeast-Atlantic cod. Site-specific analyses identified six consensus codons under positive selection, including 122β(GH5), indicating that the amino acid changes identified at this position may offer an adaptive advantage. In fact, computational mutation analysis showed that the replacement of Phe GH5 with Leu or Cys decreased the number of van der Waals contacts essentially in the deoxy form that probably causes a slight increase in the oxygen binding affinity.ConclusionsThe almost invariant Arg B12 and the AGG codon seem to be important for the packing contacts and pre-mRNA processing, respectively, but the rare mutations identified might be beneficial. The Leu122β1(GH5)Met and Met55β1(D6)Val polymorphisms in Atlantic cod hemoglobin modify the intradimer contacts B12-GH5 and H2-D6, while amino acid replacements at these positions in avian hemoglobin seem to be evolutionary adaptive in air-breathing vertebrates. The results support the theory that adaptive changes in hemoglobin functions are caused by a few substitutions at key positions.

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“…In solution, the functional properties of the αβ dimer are similar to that of the R state tetramer [13–16]. There is however a phenomenon termed quaternary enhancement based on a modest enhancement of the oxygen affinity and ligand binding properties of the αβ dimer when the dimer is incorporated into the R quaternary state of the Hb tetramer [17–24]. If the Hp bound dimer has R state functional properties, it is anticipated that the quaternary structure sensitive rate for the formation of NO from nitrite via a nitrite reductase reaction between a five coordinate ferrous heme (AKA deoxy heme) and nitrite should also be enhanced.…”

Section: Introductionmentioning

confidence: 99%

Enhanced nitrite reductase activity associated with the haptoglobin complexed hemoglobin dimer: Functional and antioxidative implications

Roche¹,

Dantsker²,

Alayash³

et al. 2012

Nitric Oxide

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The presence of acellular hemoglobin (Hb) within the circulation is generally viewed as a pathological state that can result in toxic consequences. Haptoglobin (Hp), a globular protein found in the plasma, binds with high avidity the αβ dimers derived from the dissociation of Hb tetramer and thus helps clear free Hb. More recently there have been compelling indications that the redox properties of the Hp bound dimer (Hb–Hp) may play a more active role in controlling toxicity by limiting the potential tissue damage caused by propagation of the free-radicals generated within the heme containing globin chains. The present study further examines the potential protective effect of Hp through its impact on the production of nitric oxide (NO) from nitrite through nitrite reductase activity of the Hp bound αβ Hb dimer. The presented results show that the Hb dimer in the Hb–Hp complex has oxygen binding, CO recombination and spectroscopic properties consistent with an Hb species having properties similar to but not exactly the same as the R quaternary state of the Hb tetramer. Consistent with these observations is the finding that the initial nitrite reductase rate for Hb–Hp is approximately ten times that of HbA under the same conditions. These results in conjunction with the earlier redox properties of the Hb–Hp are discussed in terms of limiting the pathophysiological consequences of acellular Hb in the circulation.

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Allosteric effects of chloride ions at the intradimeric α₁β₁ and α₂β₂ interfaces of human hemoglobin

Cited by 6 publications

References 40 publications

1.25 Å Resolution Crystal Structures of Human Haemoglobin in the Oxy, Deoxy and Carbonmonoxy Forms

1.25 Å Resolution Crystal Structures of Human Haemoglobin in the Oxy, Deoxy and Carbonmonoxy Forms

The conserved Phe GH5 of importance for hemoglobin intersubunit contact is mutated in gadoid fish

Enhanced nitrite reductase activity associated with the haptoglobin complexed hemoglobin dimer: Functional and antioxidative implications

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