Myoglobin & Hemoglobin.
This page shows some interactive JSmol views of oxygen transport and storage proteins.
The first set of views show the aquamet form of the oxygen storage protein myoglobin
(aquamet = permanently oxidised, with a bound water molecule).
The metalloprotein contains one heme group which has no direct covalent bonds to the protein chain - it
is held in place by a large number of hydrophobic interactions and by one coordinate bond, from a His residue to the
iron ion. The iron(III) ion has fairly regular 6-coordination, bound to the four N donors of the porphyrin, the
protein His residue and a water ligand.
The bound His is referred to as the "proximal histidine"; there is another, the "distal histidine", on
the other side of the porphyrin. The distal histidine is too far away to bind to the iron but is H-bonded to the
coordinated water molecule.
The "picket fence" model complex was designed to mimic the oxygen-binding site of myoglobin (or hemoglobin),
largely based on information obtained from the crystal structure of aquametMb.
The four "pickets" provide a hydrophobic pocket for dioxygen to bind and the N-methylimidazole
mimics the proximal histidine. The complex binds dioxygen reversibly in the end-on coordination mode.
The oxymyoglobin structure was published some years after the aquametMb and picket fence structures. [oxyMb 1] and
[oxyMb 2] show
dioxygen bound in the pocket where water was bound in aquametMb, with geometry similar to that seen
in the picket fence model. The distal histidine is H-bonded to the dioxygen and the site is surrounded by non-polar
residues.
In [deoxyMb 1] the iron is in the +II state and the sixth coordination site is vacant. There is an uncoordinated water molecule
in the binding cavity, H-bonded to the distal histidine but not interacting with the iron.
Note that the iron ion is no longer in the plane of the porphyrin ring but displaced towards the proximal histidine
and away from the dioxygen binding site.
The last figure in this group is carboxymyoglobin, [carboxyMb], in which carbon monoxide is bound in the dioxygen site.
It is a little difficult to see, but the Fe-C-O bond is not quite linear and not quite perpendicular
to the plane of the porphyrin ring.
The final set of figures show the deoxy and oxy forms of hemoglobin. This molecule is a tetramer containing 2
α-subunits and 2 β-subunits,
each subunit is similar to myoglobin. The first figure, [deoxyHb], shows the tetramer of deoxyHb with each subunit a
different colour. [oxyHb 1] shows oxyHb, with the α- and β-subunits coloured differently.
Binding dioxygen to Hb is accompanied by a conformational change which is the basis for the "cooperative effect".
See the animation from the PDB here (half way down the page). This movement
is initiated by the iron ion moving into the plane of the porphyrin ring when it binds dioxygen (and becomes low-spin).
The last view shows the oxyHb active site [oxyHb 2]. The features of the site are very similar to those of myoglobin.
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Picket fence model data from Structure of a dioxygen adduct of (1-methylimidazole)-meso-tetrakis (α,α,α,α,-o-pivalamidophenyl)porphinatoiron(II). An iron dioxygen model for the heme component of oxymyoglobin G.B. Jameson, G.A. Rodley, W.T. Robinson, R.R. Gagne, C.A. Reed and J.M. Collman, Inorg. Chem., 17, 850-857, 1978.
OxyMb (PDB 1LTW) data from Perturbation of the Fe-O2 Bond by Nearby Residues in Heme Pocket: Observation of fe-O2 Raman Bands for Oxymyoglobin Mutants. Hirota, S., Li, T., Phillips Jr., G.N., Olson, J.S., Mukai, M., Kitagawa, T. (1996) J.Am.Chem.Soc. 118: 7845
DeoxyHb (PDB 2HHB) data from: The crystal structure of human deoxyhaemoglobin at 1.74 A resolution. Fermi, G., Perutz, M.F., Shaanan, B., Fourme, R. (1984) J.Mol.Biol. 175: 159-174.
OxyHb (PDB 3A0G) data from: Crystal structure analysis of guinea pig oxyhemoglobin at 2.5 angstroms resolution. Etti, S., Shanmugam, G., Karthe, P., Gunasekaran, K. unpublished.
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