Global Allostery Model of Hemoglobin

The O2 equilibria of human adult hemoglobin have been measured in a wide range of solution conditions in the presence and absence of various allosteric effectors in order to determine how far hemoglobin can modulate its O2 affinity. The O2 affinity, cooperative behavior, and the Bohr effect of hemoglobin are modulated principally by tertiary structural changes, which are induced by its interactions with heterotropic allosteric effectors. In their absence, hemoglobin is a high affinity, moderately cooperative O2 carrier of limited functional flexibility, the behaviors of which are regulated by the homotropic, O2-linked T/R quaternary structural transition of the Monod-Wyman-Changeux/Perutz model. However, the interactions with allosteric effectors provide such “inert” hemoglobin unprecedented magnitudes of functional diversities not only of physiological relevance but also of extreme nature, by which hemoglobin can behave energetically beyond what can be explained by the Monod-Wyman-Changeux/Perutz model. Thus, the heterotropic effector-linked tertiary structural changes rather than the homotropic ligation-linked T/R quaternary structural transition are energetically more significant and primarily responsible for modulation of functions of hemoglobin.

[1]  T. Yonetani,et al.  Description of hemoglobin oxygenation under universal solution conditions by a global allostery model with a single adjustable parameter. , 2002, Biophysical chemistry.

[2]  J. Wyman,et al.  LINKED FUNCTIONS AND RECIPROCAL EFFECTS IN HEMOGLOBIN: A SECOND LOOK. , 1964, Advances in protein chemistry.

[3]  M Karplus,et al.  A mathematical model for structure-function relations in hemoglobin. , 1972, Journal of molecular biology.

[4]  G. Adair.  THE HEMOGLOBIN SYSTEM VI. THE OXYGEN DISSOCIATION CURVE OF HEMOGLOBIN , 1925 .

[5]  K. Imai.  The Monod-Wyman-Changeux allosteric model describes haemoglobin oxygenation with only one adjustable parameter. , 1983, Journal of molecular biology.

[6]  M Paoli,et al.  The stereochemical mechanism of the cooperative effects in hemoglobin revisited. , 1998, Annual review of biophysics and biomolecular structure.

[7]  J J Hopfield,et al.  Relation between structure, co-operativity and spectra in a model of hemoglobin action. , 1973, Journal of molecular biology.

[8]  T. Yonetani,et al.  Heterotropic effectors control the hemoglobin function by interacting with its T and R states--a new view on the principle of allostery. , 2002, Biophysical chemistry.

[9]  J. Wyman,et al.  Nuclear magnetic resonance quadrupole relaxation studies of chloride binding to human oxy- and deoxyhaemoglobin. , 1972, Journal of molecular biology.

[10]  M. Marden,et al.  Effectors of hemoglobin. Separation of allosteric and affinity factors. , 1990, Biophysical journal.

[11]  K. Imai.  Allosteric Effects in Haemoglobin , 1982 .

[12]  M. Brunori,et al.  Studies on the properties of fish hemoglobins. Molecular properties and interaction with third components of the isolated hemoglobins from trout (Salmo irideus). , 1973, European journal of biochemistry.

[13]  S. Edelstein,et al.  An expanded two-state allosteric model for interactions of human hemoglobin A with nonsaturating concentrations of 2,3-diphosphoglycerate. , 1987, The Journal of biological chemistry.

[14]  K. Imai.  Correlation between narrow-banded ultraviolet spectra and oxygen equilibrium functions in native and chemically modified human hemoglobins. , 1973, Biochemistry.

[15]  D. Drabkin,et al.  Spectrophotometric studies; the crystallographic and optical properties of the hemoglobin of man in comparison with those of other species. , 1946, The Journal of biological chemistry.

[16]  M. Karplus,et al.  Analysis of proton release in oxygen binding by hemoglobin: implications for the cooperative mechanism. , 1988, Biochemistry.

[17]  Pierre Plateau,et al.  Exchangeable proton NMR without base-line distorsion, using new strong-pulse sequences , 1982 .

[18]  C. Ho,et al.  Effects of anions and ligands on the tertiary structure around ligand binding site in human adult hemoglobin. , 1973, Biochemistry.

[19]  T. Yonetani,et al.  The hemoglobin-oxygen equilibrium associated with sub-unit dissociation I. An approach with the hill scheme , 1977 .

[20]  Xuesi Chen,et al.  Electron Paramagnetic Resonance and Oxygen Binding Studies of α-Nitrosyl Hemoglobin , 1998, The Journal of Biological Chemistry.

[21]  C. Ho,et al.  A proton nuclear Overhauser effect investigation of the subunit interfaces in human normal adult hemoglobin. , 1987, Biochimica et biophysica acta.

[22]  L. Janssen,et al.  The interaction of 2,3-diphosphoglycerate on human deoxy and oxyhemoglobin. , 1973, Biochemical and biophysical research communications.

[23]  A. Riggs.  Mechanism of the enhancement of the Bohr effect in mammalian hemoglobins by diphosphoglycerate. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[24]  K. Imai,et al.  Studies on the function of abnormal hemoglobins. I. An improved method for automatic measurement of the oxygen equilibrium curve of hemoglobin. , 1970, Biochimica et biophysica acta.

[25]  C. Cantor,et al.  Measurement of ligand-induced conformational changes in hemoglobin by circular dichroism. , 1969, Proceedings of the National Academy of Sciences of the United States of America.

[26]  P. Ascenzi,et al.  Coupling of the Oxygen-linked Interaction Energy for Inositol Hexakisphosphate and Bezafibrate Binding to Human HbA0 * , 1999, The Journal of Biological Chemistry.

[27]  T. Yonetani,et al.  PH dependence of the Adair constants of human hemoglobin. Nonuniform contribution of successive oxygen bindings to the alkaline Bohr effect. , 1975, The Journal of biological chemistry.

[28]  R. Benesch,et al.  The removal of organic phosphates from hemoglobin. , 1971, Archives of biochemistry and biophysics.

[29]  R. Edalji,et al.  Reciprocal interaction of hemoglobin with oxygen and protons. The influence of allosteric polyanions. , 1977, Biochemistry.

[30]  M. Perutz,et al.  Structure Of Hæemoglobin: A Three-Dimensional Fourier Synthesis of Reduced Human Haemoglobin at 5.5 Å Resolution , 1963, Nature.

[31]  A. Minton,et al.  The three-state model: a minimal allosteric description of homotropic and heterotropic effects in the binding of ligands to hemoglobin. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[32]  R. Stepnoski,et al.  The iron-proximal histidine linkage and protein control of oxygen binding in hemoglobin. A transient Raman study. , 1983, The Journal of biological chemistry.

[33]  Max F. Perutz,et al.  Hemoglobin as a receptor of drugs and peptides: x-ray studies of the stereochemistry of binding , 1986 .

[34]  M. Perutz,et al.  BEZAFIBRATE LOWERS OXYGEN AFFINITY OF HAEMOGLOBIN , 1983, The Lancet.

[35]  D. Koshland,et al.  Comparison of experimental binding data and theoretical models in proteins containing subunits. , 1966, Biochemistry.

[36]  J F Murray,et al.  Determination of sulfhydryl groups with 2,2'- or 4,4'-dithiodipyridine. , 1967, Archives of biochemistry and biophysics.

[37]  C. Lenfant,et al.  Effect of altitude on oxygen binding by hemoglobin and on organic phosphate levels. , 1968, The Journal of clinical investigation.

[38]  Andrea Mozzarelli,et al.  Is cooperative oxygen binding by hemoglobin really understood? , 1999, Nature Structural Biology.

[39]  M. Marden,et al.  T-state hemoglobin with four ligands bound. , 1988, Biochemistry.

[40]  C. Ho,et al.  Proton nuclear Overhauser effect investigation of the heme pockets in ligated hemoglobin: conformational differences between oxy and carbonmonoxy forms. , 1985, Biochemistry.

[41]  K. Nagai,et al.  Quaternary structures and low frequency molecular vibrations of haems of deoxy and oxyhaemoglobin studied by resonance raman scattering. , 1980, Journal of molecular biology.

[42]  E. Henry,et al.  Oxygen binding by single crystals of hemoglobin. , 1993, Biochemistry.

[43]  K. Imai,et al.  The linkage between the four-step binding of oxygen and the binding of heterotropic anionic ligands in hemoglobin. , 1979, Journal of biochemistry.

[44]  M Karplus,et al.  Hemoglobin tertiary structural change on ligand binding. Its role in the co-operative mechanism. , 1983, Journal of molecular biology.

[45]  Non-linear relationships between oxygen saturation and magnitude of fine structure of ultraviolet oxy versus deoxy difference spectrum in human hemoglobin. , 1973, Biochemical and biophysical research communications.

[46]  K. Imai,et al.  Physicochemical studies of the relation between structure and function in hemoglobin Hiroshima (HC3 , histidine leads to aspartate). , 1972, Biochemistry.

[47]  M. Perutz.  Stereochemistry of Cooperative Effects in Haemoglobin: Haem–Haem Interaction and the Problem of Allostery , 1970, Nature.

[48]  G. K. Ackers.  The energetics of ligand-linked subunit assembly in hemoglobin require a third allosteric structure. , 1990, Biophysical chemistry.

[49]  L. Janssen,et al.  Effect of 2,3-diphosphoglycerate on the Bohr effect of human adult hemoglobin. , 1971, Biochemical and biophysical research communications.

[50]  J. Changeux,et al.  ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL. , 1965, Journal of molecular biology.

[51]  S. Edelstein,et al.  Oxygen-organophosphate linkage in hemoglobin A. The double hump effect. , 1987, Biophysical journal.