Oxygen equilibrium properties of asymmetric nickel(II)-iron(II) hybrid hemoglobin

Shibayama, Naoya; Imai, Katsunori; Morimoto, Hideki; Saigo, Satoshi

doi:10.1021/bi00085a009

Cited by 26 publications

(26 citation statements)

References 47 publications

(76 reference statements)

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“…Also unlike HbA, no major quaternary changes occur upon binding of oxygen to HbI (the heavy-atom RMSD between the liganded and unliganded structure of HbI is 1.3 Å ), and the tertiary structural changes are small and localized near the heme group. Nevertheless, HbI is highly cooperative; the binding of oxygen to its two equivalent binding sites has a Hill coefficient of 1.5 (Chiancone et al 1981;Ikeda-Saito et al 1983), similar to the value (1.36-1.72) for human hemoglobin (HbA) when two of the Fe +2 are replaced by nonreactive Ni +2 (Shibayama et al 1993). Thus, the mechanism of cooperativity must be very different from that of the vertebrate hemoglobins described above.…”

Section: Cooperativity In Dimeric Hemoglobin: Water-mediated Allostermentioning

confidence: 91%

Allostery and cooperativity revisited

2008

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Although phenomenlogical models that account for cooperativity in allosteric systems date back to the early and mid-60's (e.g., the KNF and MWC models), there is resurgent interest in the topic due to the recent experimental and computational studies that attempted to reveal, at an atomistic level, how allostery actually works. In this review, using systems for which atomistic simulations have been carried out in our groups as examples, we describe the current understanding of allostery, how the mechanisms go beyond the classical MWC/Pauling-KNF descriptions, and point out that the ''new view'' of allostery, emphasizing ''population shifts,'' is, in fact, an ''old view.'' The presentation offers not only an up-to-date description of allostery from a theoretical/computational perspective, but also helps to resolve several outstanding issues concerning allostery.

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Section: Cooperativity In Dimeric Hemoglobin: Water-mediated Allostermentioning

confidence: 91%

Allostery and cooperativity revisited

2008

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“…Since the nickel atoms remain five-coordinated, they stabilize the T-structure. Shibayama et al found the average K 1 s of the nickel-iron hybrids to be close to the first Adair constant of normal human hemoglobin, which suggested that permutations of such hybrids could serve as models of intermediates in the reactions of hemoglobins with ligands (48,49).…”

Section: Incompatibility With Free Energy Of Cooperativitymentioning

confidence: 99%

The Stereochemical Mechanism of the Cooperative Effects in Hemoglobin Revisited

Perutz

Wilkinson

Paoli

et al. 1998

Annu. Rev. Biophys. Biomol. Struct.

528

524

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In 1970, Perutz tried to put the allosteric mechanism of hemoglobin, proposed by Monod, Wyman and Changeux in 1965, on a stereochemical basis. He interpreted their two-state model in terms of an equilibrium between two alternative structures, a tense one (T) with low oxygen affinity, constrained by salt-bridges between the C-termini of the four subunits, and a relaxed one (R) lacking these bridges. The equilibrium was thought to be governed primarily by the positions of the iron atoms relative to the porphyrin: out-of-plane in five-coordinated, high-spin deoxyhemoglobin, and in-plane in six-coordinated, low-spin oxyhemoglobin. The tension exercised by the salt-bridges in the T-structure was to be transmitted to the heme-linked histidines and to restrain the movement of the iron atoms into the porphyrin plane that is necessary for oxygen binding. At the beta-hemes, the distal valine and histidine block the oxygen-combining site in the T-structure; its tension was thought to strengthen that blockage. Finally, Perutz attributed the linearity of proton release with early oxygen uptake to the sequential rupture of salt-bridges in the T-structure and to the accompanying drop in pKa of the weak bases that form part of them. Almost every feature of this mechanism has been disputed, but evidence that has come to light more than 25 years later now shows it to have been substantially correct. That new evidence is reviewed below.

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“…To represent the oxygenation intermediates of Hb A, the hybrids in group (i) and (iii) are particularly important. In our recent series of studies, Ni(II)-Fe(II) hybrid Hbs in group (iii) have been used successfully to investigate the structures and functions of the intermediates appearing in the first half oxygenation of Hb A (21)(22)(23)(24)(25)(26)(27)(28). Although the Ni(II)-Fe(II) hybrid system has brought much structural and functional information about the initial-half oxygenated intermediates, this approach could not be extended to studies on the latter-half oxygenation of Hb A.…”

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confidence: 99%

Oxygen Equilibrium Properties of Chromium(III)-Iron(II) Hybrid Hemoglobins

Unzai

Hori

Miyazaki

et al. 1996

Journal of Biological Chemistry

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Cr(III)-Fe(II) hybrid hemoglobins, ␣ 2 (Cr)␤ 2 (Fe) and ␣ 2 (Fe)␤ 2 (Cr), in which hemes in either the ␣-or ␤-subunits were substituted with chromium(III) protoporphyrin IX (Cr(III)PPIX), were prepared and characterized by oxygen equilibrium measurements. Because Cr(III)PPIX binds neither oxygen molecules nor carbon monoxide, the oxygen equilibrium properties of Fe(II) subunits within these hybrids can be analyzed by a twostep oxygen equilibrium scheme. The oxygen equilibrium constants for both hybrids at the second oxygenation step agree with those for human adult hemoglobin at the last oxygenation step (at pH 6.5-8.4 with and without inositol hexaphosphate at 25°C). The similarity between the effects of the Cr(III)PPIX and each subunits' oxyheme on the oxygen equilibrium properties of the counterpart Fe(II) subunits within hemoglobin indicate the utility of Cr(III)PPIX as a model for a permanently oxygenated heme within the hemoglobin molecule.We found that Cr(III)-Fe(II) hybrid hemoglobins have several advantages over cyanomet valency hybrid hemoglobins, which have been frequently used as a model system for partially oxygenated hemoglobins. In contrast to cyanomet heme, Cr(III)PPIX within hemoglobin is not subject to reduction with dithionite or enzymatic reduction systems. Therefore, we could obtain more accurate and reasonable oxygen equilibrium curves of Cr(III)-Fe(II) hybrids in the presence of an enzymatic reduction system, and we could obtain single crystals of deoxy-␣ 2 (Cr)␤ 2 (Fe) when grown in low salt solution in the presence of polyethylene glycol 1000 and 50 mM dithionite. Human adult hemoglobin (Hb A)1 cooperatively binds four oxygen molecules via a complex sequence of intermediate oxygenated states. Information about the intermediate species is required to understand the cooperative mechanism of Hb A, yet little is known about such intermediates because the equilibrium concentrations of the intermediates under any conditions are markedly reduced by the cooperativity of Hb.Cyanomet valency hybrid Hbs have been frequently used for studying the oxygenation intermediates of Hb A (1-12). Structural and functional studies on cyanomet valency hybrids have suggested that cyanide-bound ferric heme mimics natural oxyheme, thus deoxy-cyanomet valency hybrid Hbs have been used as models for the intermediate species formed during the cooperative oxygenation process (13)(14)(15)(16)(17)(18)(19)(20). However, since conventional met-Hb reducing reagents and enzymatic reduction systems reduce the cyanomet heme, it is very difficult to carry out the experiments using deoxy-cyanomet valency hybrids under anaerobic conditions. Thus, there have been no reports on x-ray crystallography of cyanomet valency hybrids because of this difficulty.During recent years, we have investigated the properties of metal-substituted hybrid Hbs, ␣ 2 (M)␤ 2 (Fe) and ␣ 2 (Fe)␤ 2 (M), using the first transition metal ions (M). This metal substitution method is the most suitable modification of Hb A for studying the relationships between...

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Oxygen equilibrium properties of asymmetric nickel(II)-iron(II) hybrid hemoglobin

Cited by 26 publications

References 47 publications

Allostery and cooperativity revisited

Allostery and cooperativity revisited

The Stereochemical Mechanism of the Cooperative Effects in Hemoglobin Revisited

Oxygen Equilibrium Properties of Chromium(III)-Iron(II) Hybrid Hemoglobins

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