Heme Proteins

Wyman, Jeffries

doi:10.1016/s0065-3233(08)60011-x

Cited by 596 publications

(216 citation statements)

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“…In this respect, works by Adair (1) and Wyman (2,3) paved the way to a field of investigation which became explosive when Perutz and Kendrew solved for the first time the three-dimensional structure of myoglobin (Mb) (4) and hemoglobin (Hb) (5).…”

Section: Introductionmentioning

confidence: 99%

Multiple strategies for O2 transport: from simplicity to complexity

et al. 2007

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SummaryO 2 carriers (extracellular and intracellular as well as monomeric and multimeric) have evolved over the last billion of years, displaying iron and copper reactive centers; very different O 2 carriers may coexist in the same organism. Circulating O 2 carriers, faced to the external environment, are responsible for maintaining an adequate delivery of O 2 to tissues and organs almost independently of the environmental O 2 partial pressure. Then, intracellular globins facilitate O 2 transfer to mitochondria sustaining cellular respiration. Here, molecular aspects of multiple strategies evolved for O 2 transport and delivery are examined, from the simplest myoglobin to the most complex giant O 2 carriers and the red blood cell, mostly focusing on the aspects which have been mainly addressed by the so called 'Rome Group'.

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Section: Introductionmentioning

confidence: 99%

Multiple strategies for O2 transport: from simplicity to complexity

et al. 2007

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“…As Wyman (11) recognized nearly 50 years ago, cooperative interaction energy may be present as stabilizing energy between unliganded subunits (quaternary constraint; Ref. 12) or liganded subunits (quaternary enhancement; Ref.…”

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confidence: 99%

Ligand Linked Assembly of Scapharca Dimeric Hemoglobin

Royer¹,

Fox²,

Smith³

et al. 1997

Journal of Biological Chemistry

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The assembly of Scapharca dimeric hemoglobin as a function of ligation has been explored by analytical gel chromatography, sedimentation equilibrium, and oxygen binding experiments to test the proposal that its cooperativity is based on quaternary enhancement. This hypothesis predicts that the liganded form would be assembled more tightly into a dimer than the unliganded form and that dissociation would lead to lower oxygen affinity. Our experiments demonstrate that although the dimeric interface is quite tight in this hemoglobin, dissociation can be clearly detected in the liganded states with monomer to dimer association constants in the range of 10 8 M ؊1 for the CO-liganded state and lower association constants measured in the oxygenated state. In contrast, the deoxy dimer shows no detectable dissociation by analytical ultracentrifugation. Thus, the more highly hydrated deoxy interface of this dimer is also the more tightly assembled. Equilibrium oxygen binding experiments reveal an increase in oxygen affinity and decrease in cooperativity as the concentration is lowered (in the M range). These experiments unambiguously refute the hypothesis of quaternary enhancement and indicate that, as in the case of human hemoglobin and other allosteric proteins, quaternary constraint underlies cooperativity in Scapharca dimeric hemoglobin.To perform biological activities efficiently, protein molecules have often evolved mechanisms to couple functionally independent subunits. Such cooperative activity is known to be involved in the regulation of many protein functions including enzyme activity (1, 2), gene expression (3, 4), and oxygen transport (5, 6). Much of our understanding of this process has come from studies of mammalian hemoglobins (5, 6), for which cooperativity manifests itself as a stepwise increase in oxygen affinity as oxygen binding proceeds.A particularly simple system for exploring cooperative protein function is the dimeric hemoglobin found in the blood clam Scapharca inaequivalvis, which binds oxygen with a Hill coefficient of 1.5 and shows no change in oxygen affinity or cooperativity as pH varies from 5.5 to 9.0 (7). Although the tertiary structure of the subunits is similar to those of mammalian hemoglobins, the assembly into a cooperative complex is radically different (8). High resolution crystal structure analysis of Scapharca dimeric hemoglobin (HbI) 1 has shown that ligand binding is coupled with significant tertiary rearrangements but very small quaternary changes in the relative subunit dispositions (9, 10).Intersubunit communication depends upon coupling ligand binding with interactions between subunits. As Wyman (11) recognized nearly 50 years ago, cooperative interaction energy may be present as stabilizing energy between unliganded subunits (quaternary constraint; Ref. 12) or liganded subunits (quaternary enhancement; Ref. 13). These alternate conditions can be distinguished either by measuring the strength of the subunit interface as a function of ligation or by following ligand affinity...

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“…which correlates (i) the dependence of the charge of the protein (X) on O 2 saturation (Y) with (ii) the O 2 affinity (log p 1/2 ) as a function of pH [4]. The agreement was quite satisfactory.…”

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confidence: 74%

“…7 and 8]. In addition, the so-called redox Bohr effect (extensively analyzed by Wyman and by Pauling) is the same as the O 2 Bohr effect [4], although ferric Hb, the product of oxidation of deoxy, is also paramagnetic. But possibly even more convincing was the result obtained by Riggs [20], working at Harvard for his PhD, that the two Hbs from the bullfrog are characterized by the same Hill coefficient (n ¼ 2.8) yet the adult has full Bohr effect while the tadpole Hb has none; Wyman and Allen [18] wrote: ''......it is to be expected that different Hbs, differing in the structure of the polypeptide chains, should have different Bohr effects.''…”

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confidence: 99%

“…The objection they highlighted and discussed was the puzzling observation that the shape of the O 2 binding curve was essentially pH independent, contrary to expectation based on linkage. This inconsistency was tentatively by-passed by an explanation based on a ''rectangular model'' for cooperativity, with fairly strong interactions within each dimer and much weaker ones between dimers [4], which proved incorrect many years later. In fact much more accurate data by Imai [21] have shown that the O 2 binding curve of human Hb is pH dependent, but mostly at the extremes of the saturation curve.…”

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confidence: 99%

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The BOHR effect before Perutz

Brunori

2012

Biochem Molecular Bio Educ

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Before the outbreak of World War II, Jeffries Wyman postulated that the Bohr effect in hemoglobin demanded the oxygen linked dissociation of the imidazole of two histidines of the polypeptide. This proposal emerged from a rigorous analysis of the acid–base titration curves of oxy‐ and deoxy‐hemoglobin, at a time when the information on the chemistry and structure of the protein was essentially nil. The magnetochemical properties of hemoglobin led Linus Pauling to hypothesize that the (so called) Bohr histidines were coordinated to the heme iron in the fifth and sixth positions; and Wyman shared this opinion. However, this structural hypothesis was abandoned in 1951 when J. Wyman and D. W. Allen proposed the pK shift of the oxygen linked histidines to be the result of “…a change of configuration of the hemoglobin molecule as a whole accompanying oxygenation.” This shift in paradigm, that was published well before the 3D structure of hemoglobin was solved by M.F. Perutz, paved the way to the concept of allostery. After 1960 the availability of the crystallographic structure opened new horizons to the interpretation of the allosteric properties of hemoglobin.

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Heme Proteins

Cited by 596 publications

References 155 publications

Multiple strategies for O2 transport: from simplicity to complexity

Multiple strategies for O2 transport: from simplicity to complexity

Ligand Linked Assembly of Scapharca Dimeric Hemoglobin

The BOHR effect before Perutz

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