ALLOSTERIC INTERMEDIATES INDICATE R2 IS THE LIGANDED HEMOGLOBIN END STATE

`Hemoglobin has been a long-standing paradigm for understanding protei n allostery, Here, the x-ray structures of two chemically crosslinked, fully liganded hemoglobins, alpha(2) beta(82)CA(82)beta and alpha(2) beta(82)ND(82)beta, are described at 2.3 Angstrom and 2.6 Angstrom res olution, respectively, Strikingly, these crosslinked hemoglobins assum e intermediate conformations that lie between those of R and the contr oversial liganded hemoglobin state R2 rather than between R and T. Thu s, these structures support only a T <-> R <-> R2 allosteric pathway a nd underscore the physiological importance of the R2 conformation.