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A New Dimer‐based Model of Cooperative Oxygen Release by Human Hemoglobin
Author(s) -
Ackers Gary K,
Holt Jo M
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a52-c
Subject(s) - tetramer , dimer , cooperativity , chemistry , cooperative binding , ligand (biochemistry) , crystallography , stereochemistry , binding site , biochemistry , receptor , organic chemistry , enzyme
Complete oxygenation of the hemoglobin tetramer generates eight unique partially‐ligated intermediates and involves a total of 16 binding steps. The free energy of cooperative ligand binding for each of the 16 binding steps reflects the structural organization of the molecule as a dimer of αβ dimers. A cooperative free energy potential can therefore be assigned to each subunit of the tetramer in each intermediate species. This approach enables the separation of variables with respect to dimer‐dimer vs. intradimer coupling within the tetramer. This is now possible because intradimer coupling (i.e., within the α 1 β 1 dimer or the α 2 β 2 dimer) can be observed while simultaneously monitoring the cooperative free energy potential of the hemesites in the partner dimer, and, likewise, cross‐dimer coupling (i.e., across the dimer‐dimer interface) can be assessed in the context of intradimer effects. The cooperative free energy potentials are model‐independent, and so a mechanistic model is proposed which incorporates both intradimer and dimer‐dimer cooperativity in the ligation process. The new model views intradimer coupling as fundamental to cooperativity, and does not incorporate usage of the quaternary terms T and R. The new model, which is based on model‐independent values of intermediate binding constants, is entirely consistent with native O 2 binding isotherms. The relationship of this dimer‐based model to the Symmetry Rule model is discussed. Supported by the NIH.