Hemoglobin Protein Dynamics

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Oxy to Deoxyhemoglobin transition: molecular motion

• Oxy-to-deoxyhemoglobin structural transition is illustrated by description of the motion of the ₂ß₂dimer (thick coils towards front) relative to the₁ß₁dimer (thin coils towards rear). Molecular coordinates of oxy- and deoxy-Hb have been superimposed at the ₁ß₁ interface and the ₁ß₁dimer remains stationary.  The transition is characterized by an ₂ß₂dimer by a 15 degree rotatation about an  axis passing through the subunits. Animation and description courtesy of Dr. John Lukin, Dept. of Biological Sciences, Carnegie Mellon University, used with permission

Histidine Structure

• Illustration of the subunit heme together with the proximal Histidine . In the oxy-to-deoxy transition, the iron atom transitions from a location in the heme plane to a position above in and in the process displaces the proximal His. Animation and description courtesy of Dr. John Lukin, Dept. of Biological Sciences, Carnegie Mellon University, used with permission.

• Residues, within 8 Å of the two-fold axis of Hb, are represented.  These residues define a central cavity in hemoglobin and this cavity enlarges dramatically upon deoxygenation. Note the motion of the C-terminal Histidines of ß₁and ß₂ , towards the upper and lower edges of the figure, respectively. The C-terminal Arginines of the subunits also move apart significantly, towards the upper left and lower right corners,  in front of the subunits in the figure. 

• The effector (2,3)-DPG binds to positively-charged subunit residues in the central cavity domain. While (2,3)-DPG is too large to fit into the narrow cavity of oxy-Hb, it binds readily in the larger cavity of the deoxy conformation. Thus, (2,3)-DPG binding lowers the oxygen affinity of Hb by shifting the oxy-deoxy structural distribution of the protein in a manner that favors the deoxy state.  The physiological consequence of 2,3 DPG modulation has been discussed above. Animation and description courtesy of Dr. John Lukin, Dept. of Biological Sciences, Carnegie Mellon University, used with permission. (http://www.andrew.cmu.edu/user/jl2p/Hb_html/gallery.html)

Central Cavity in deoxyhemoglobin which defines the DPG binding location

Note the reduced central cavity size in oxyhemoglobin with attendant prevention of DPG binding (http://www.udel.edu/chem/bahnson/Chem641/chime/Index.htm)

• Oxy to Deoxy transition above emphasizes the ß subunit view  of the heme moiety (shown as a set of flat plates) face-on and illustrates residues in the proximal side of the heme pocket. "Note the tilt of the proximal Histidine (ß His92) and the resulting translational motion of the attached Leucine." Animation and description courtesy of Dr. John Lukin, Dept. of Biological Sciences, Carnegie Mellon University, used with permission.

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• ⁵⁴Dr. John Lukin, Dept. of Biological Sciences, Carnegie Mellon University,  (http://www.andrew.cmu.edu/user/jl2p/Hb_html/gallery.html)