The “Caged” State, the Transition State of the Regulation of Oxygen-Affinity in Hemoglobin

The “caged” state of hemoglobin (Hb) and cobalt-substituted Hb (Co-Hb) is produced by cryogenic photolysis of respective hemoproteins at 4.2K [1-4]. The “caged” state of oxy-Hb and oxy-CoHb, in which the heme-oxygen bond is broken and the un-bonded oxygen is trapped in or near the heme pocket within the globin moiety, with spectral features distinct from those of either deoxy- or ligated states of respective hemoproteins, is the critical transition state in the regulation of the oxygen-affinity of Hb and CoHb. The oxygen-affinity of Hb is regulated by heterotropic effectors without detectable changes in either static quaternary/tertiary molecular structures of the protein or the coordination/electronic structures of the hemes and, thus, without changes in the oxygen-affinity of the heme Fe itself [5,6,8]. The reduction of the apparent oxygen-affinity of Hb may be caused by increase in the dissociation rate of oxygen from the “caged” state, resulting from effector-linked, enhanced high-frequency thermal fluctuations [6-8], which may simultaneously reduce the rate of geminate-recombination of oxygen to hemes. Thus, the oxygen-affinity of Hb is regulated by protein dynamics, rather than static structural changes. Thus, the “caged” state of Hb is the pivotal point in regulation of the affinity for small diatomic ligands such as oxygen, CO, and NO of Hb and Co-Hb [8].References: [1] Yonetani, et al., Oxidases & Related Redox Systems, Vol. I, ed. T.E. King et al. (1973) pp. 401-405; [2] Iizuka, et al., BBA 351 (1974) 182-195; [3] Iizuka, et al., BBA 371(1974) 126-139; [4] Yonetani, et al., JBC 249 (1974) 2168-2174; [5] Yonetani, et al., JBC 277 (2002) 34508-34520; [6] Yonetani & Laberge, BBA 1784 (2008) 1146-1158; [7] Laberge & Yonetani, Biophys. J. 94 (2008) 2737-2751; [8] Yonetani & Kanaori, BBA 1834 (2013) 1873-1884.