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- W3199050545 endingPage "101024" @default.
- W3199050545 startingPage "101024" @default.
- W3199050545 abstract "Antonini and Brunori's 1971 book “Hemoglobin and Myoglobin in Their Reactions with Ligands” was a truly remarkable publication that summarized almost 100 years of research on O2 binding to these globins. Over the ensuing 50 years, ultra-fast laser photolysis techniques, high-resolution and time resolved X-ray crystallography, molecular dynamics simulations, and libraries of recombinant myoglobin (Mb) and hemoglobin (Hb) variants have provided structural interpretations of O2 binding to these proteins. The resultant mechanisms provide quantitative descriptions of the stereochemical factors that govern overall affinity, including proximal and distal steric restrictions that affect iron reactivity and favorable positive electrostatic interactions that preferentially stabilize bound O2. The pathway for O2 uptake and release by Mb and subunits of Hb has been mapped by screening libraries of site-directed mutants in laser photolysis experiments. O2 enters mammalian Mb and the α and β subunits of human HbA through a channel created by upward and outward rotation of the distal His at the E7 helical position, is non-covalently captured in the interior of the distal cavity, and then internally forms a bond with the heme Fe(II) atom. O2 dissociation is governed by disruption of hydrogen bonding interactions with His (E7), breakage of the Fe(II)–O2 bond, and then competition between rebinding and escape through the E7-gate. The structural features that govern the rates of both the individual steps and overall reactions have been determined and provide the framework for: (1) defining the physiological functions of specific globins and their evolution; (2) understanding the clinical features of hemoglobinopathies; and (3) designing safer and more efficient acellular hemoglobin-based oxygen carriers (HBOCs) for transfusion therapy, organ preservation, and other commercially relevant O2 transport and storage processes." @default.
- W3199050545 created "2021-09-27" @default.
- W3199050545 creator A5017318009 @default.
- W3199050545 date "2022-04-01" @default.
- W3199050545 modified "2023-10-17" @default.
- W3199050545 title "Kinetic mechanisms for O2 binding to myoglobins and hemoglobins" @default.
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