A Tour of Myoglobin

Please be patient while the structures in the left frame load. In order to display all the structures in the tour properly, press 'View' buttons below in order (from 1 to the end).

Crystals of myoglobin

Crystals of myoglobin grown on the MIR space station. For more details see MIR Protein Crystal Growth Program (Sorry, this web address does not exist any longer...)

Myoglobin is a simple oxygen transport protein. Oxygen is carried to the myoglobin via hemoglobin. It is then released to the muscle cells for respiration.

Myoglobin is generally found in muscle tissues of vertebrates. It consists of a single polypeptide chain of 153 amino acids called globin. This chain is made up of seven alpha helical and six non-helical segments. The helical segments are designated with letters A through H.

The prosthetic group in myoglobin is protoporphyrin IX shown here in ball and stick representation. In the centre of this group resides the iron ion. An iron-porphyrin group is called a heme. In myoglobin, the heme group is located in the ‘V’ shaped pocket between helices E and F (red). The oxygen is coloured in red, nitrogen is coloured in blue, iron(II) is coloured in light brown.

This structure shows an enlarged active site.

Histidine 93 (blue) also known as the proximal histidine, is the only connection of heme group with the protein. It is located on the helix F. This amino acid is covalently bonded to the iron ion.

Another histidine residue (His64, blue-gray) enters the pocket from helix E. Since this histidine molecule is not bonded to heme iron, it is called the distal histidine.

An additional amino acid, valine (Val68, green) also enters the heme pocket from the helix E. It is not bonded to the iron centre but there is evidence that it plays an important role in CO vs O2 discrimination. (See below.)

This is the representation of the deoxy-myoglobin core. It can be seen that the iron(II) center is pentacoordinate. Note the distance between Fe and N atom in His 64. This metal atom lies 0.42 Å out of the plane of the four pyrrole-ring donor nitrogens in protoporphyrin IX. It can be seen that it is displaced towards the bonded imidazole group on the proximal side. You will be able to see this displacement better if you change the display on the left to wireframe or stick.

Upon binding of the dioxygen, iron adopts an octahedral coordination geometry. The iron atom moves towards the porphyrin plane. In oxy-myoglobin, the dioxygen molecule is bonded end-on to iron, forming a bent structure with an Fe-O-O bond angle of 115°. The distal histidine (His64) forms an N-H...O hydrogen bond with the dioxygen ligand, further stabilizing the structure.

This shows the coordination of carbon monoxide to the iron. The coordination of CO to the iron ion is defined by repulsive interactions of the CO oxygen with distal residues His64 and Val68. Note the short distances between Val68, His64 and oxygen in the carbonyl ligand. Since the whole pocket formed by helices E and F is rigid, it does not allow much movement in the position of the Val68 so that the Fe-C-O axis has to tilt away from the normal to the plane of the porphyrin. This tilt weakens the Fe-CO bond and destabilizes the complex.

You can see this steric effect better here the with carbonyl, val68 and his64 displayed in space-filled mode. Note how valine "intrudes" CO "space".

This is the wireframe display of myoglobin structure. Feel free to play with it using the controls that are accessed by clicking on the structure.

The crystal structures of deoxy- and CO-myoglobin by Kachalova, G.S. et al. Science, 284 (1999) 473 (PDB IDs 1BZP and 1BZR). The crystal structure of oxy-myoglobin by Vojtechovsky, J. et al. (to be published, PDB ID 1A6M)

Myoglobin – A Model Compound

In order to gain a better insight on how myoglobin discriminates between O2 and CO, model systems have been developed.

The main synthetic challenge represents the synthesis of a pentacoordinated iron(II) complex with a sixth coordination site hindered to prevent Fe(III)-OO-Fe(III) bridging.

One of the ligands that can give this geometry is shown here. It is nicknamed a "picket fence" porphyrin. One face of the porphyrin ring is hindered by four o-pivalamidophenyl groups located on positions 5, 10, 15 and 20 of porphyrin ring.

This is the structure of a "deoxy" model complex. [1] 2-methylimidazole occupies the fifth coordination place on the iron(II) ion at the bottom of the ring and plays the role of the proximal histidine. The "fence" effectively protects sixth coordination site having the effect similar to that of the distal histidine and valine 68. In this complex iron also lies approximately 0.4 angstroms out of the plane of the tetradentate ring. It is displaced towards the imidazole ligand. This can be seen better if you change the view to stick or wireframe.

This is the structure of a "oxy" model complex.[2]. Small molecules, like O2, can still reach the iron center. Much like in oxy myoglobin, the O2 molecule binds end-on to the Fe(II) ion. You'll note that there are actually three O atoms around the metal centre. This is due to the disorder in the structure. The disorder occurs because the dioxygen molecule adopts at least two orientations with respect to a rotation around the Fe - O bond, even in the solid state. The X-ray single crystal analysis "picks up" only the average. Hence the exact position of the second oxygen atom cannot be precisely determined.

Other substituted porphyrin ligands have also been developed.

This is the structure of a CO-myoglobin model complex[3]. It contains a so-called “capped” porphyrin ligand [4]. This “cap”, like dome, almost completely hinders one side of the ring causing severe distortions in the structure of carbonyl complex.

If you want to learn more about myoglobin models see:

div101 (1K)

[1] Jameson, G.B. et al. J. Am. Chem. Soc. 102 (1980) 3224

[2] Jameson, G.B. et al. ibid

[3] Kim, K. et al. J. Am. Chem. Soc. 111 (1989) 403

[4] Collman et al J. Am. Chem. Soc. 103 (1981) 2450

Copyright Robert H. Morris, Adrian Lee and Alen Hadzovic, 1998, 2009, 2011.