title: Global allostery model of hemoglobin. Modulation of O(2) affinity, cooperativity, and Bohr effect by heterotropic allosteric effectors.
abstract: The O(2) 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 O(2) affinity. The O(2) 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 O(2) carrier of limited functional flexibility, the behaviors of which are regulated by the homotropic, O(2)-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.
authors.affiliation: Department of Biochemistry and Biophysics, and Johnson Research Foundation, University of Pennsylvania Medical Center, 3600 Hamilton Walk, Philadelphia, PA 19104-6059, USA. yonetant@mail.med.upenn.edu
authors.forename: Takashi
authors.initials: T
authors.lastname: Yonetani
authors.forename: Sung-Ick
authors.initials: SI
authors.lastname: Park
authors.forename: Antonio
authors.initials: A
authors.lastname: Tsuneshige
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Imai
authors.forename: Kenji
authors.initials: K
authors.lastname: Kanaori
mesh_terms: D000494:Allosteric Regulation; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008961:Models, Structural; D010100:Oxygen / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D006454:Hemoglobins; D010100:Oxygen