Myoglobin

Myoglobin is a muscle heteroprotein, structurally and functionally very similar to hemoglobin. It is a relatively small protein made up of a polypeptide chain of 153 amino acid residues and a heme group containing a iron atom. The function of myoglobin is to store oxygen. Less commonly it has also been called myohemoglobin or muscle hemoglobin.

The highest concentrations of myoglobin are found in skeletal muscle and cardiac muscle, where large amounts of O₂ are required to meet the energy demands of contractions.

Myoglobin was the first protein whose three-dimensional structure was determined experimentally. In 1958, John Kendrew and his colleagues determined the structure of myoglobin using high-resolution X-ray crystallography. For this discovery, John Kendrew was awarded the Nobel Prize in Chemistry in 1962, shared with Max Perutz.

It is an extremely compact and globular protein, in which most of the hydrophobic amino acids are found inside and many of the polar residues are exposed on the surface. About 78% of the secondary structure has an alpha-helix conformation; in fact, there are eight alpha-helix segments in myoglobin, designated A through H.

Inside a hydrophobic cavity of the protein is the heme prosthetic group. This non-polypeptide unit is non-covalently bound to myoglobin and is essential for the O₂ binding biological activity of the protein.

Myoglobin and cytochrome B562 are part of the haem proteins, which are involved in oxygen transport and fixation, electron transport and photosynthesis. These proteins have as a prosthetic group a cyclic tetrapyrrole or heme group, or heme, formed by four planar pyrrole rings linked by alpha methylene bridges. In the center of this ring there is a ferrous iron (Fe⁺²). In the case of cytochrome, the oxidation and reduction of the iron atom are essential for biological activity. Conversely, the biological activity of myoglobin and hemoglobin is lost if Fe⁺² is oxidized.

In unoxygenated myoglobin, the heme iron lies approximately 0.03 nm out of the plane of the cluster toward the HisF8 histidine residue. Oxygenation of myoglobin produces movement of the iron atom, since oxygen occupies the sixth coordination position of iron and displaces the HisF8 residue 0.01nm out of the plane of heme.

This movement of HisF8 produces the conformational change of some regions of the protein, which favors the release of oxygen in oxygen-deficient cells, where oxygen is required for ATP-dependent metabolic energy generation.

Oxygen binding to the heme group

The ability of myoglobin and hemoglobin to bind oxygen depends on the heme group, which also gives hemoglobin and myoglobin their characteristic red color.

The heme group consists of an organic part and an iron atom. The organic part is protoporphyrin IX, formed by four pyrrole groups. The four pyrroles are linked by metene bridges to form a tetrapyrrole ring. Four methyl groups, two vinyl groups, and two propionate chains are attached to this ring.

The iron atom in heme is attached to the four nitrogens in the center of the protoporphyrin ring. Iron can form two covalent bonds with two nitrogens and two bonds which are non-covalent or coordinated bonds with the other two nitrogens and also with the histidines present at position 64 and 93 which hold the pyrrole ring, one on each side of the heme plane. These places are called the fifth and sixth coordination positions. The fifth position coordinates with a histidine residue in the hemoglobin F helix (proximal histidine), while the sixth position is occupied by oxygen. Near where the oxygen binds to the heme group is another histidine (distal histidine). The iron atom in heme can be in the ferrous (+2) or ferric (+3) oxidation state.

Myoglobin protein, first described in 1973 by H.C. watson and john kendrew.PDB-ID: 1MNBIn this representation of the structure we observe a clear predominance of the α-hylice secondary structures, specifically 8 segments (represented in cian) joined by twists (magenta). The hemo prosthetic group or cyclic tetrapirrol (magenta) is associated in a non-covalent way to the hydrophobic cleft that forms between the E and F propellers when the protein adopts its native conformation. In the center of this ring there is a ferrous iron (Fe+2, in ochre color) that is coordinated with 4 nitrogen atoms of poriforin, a N of the lateral chain of the proximal histidine F8(HIS 93) and as 6th ligand a hydroxyl group (OH, oxygen in red), near the latter ligand we observe distal histidine (HIS 93).

The corresponding forms of hemoglobin are called ferrohemoglobin and ferrihemoglobin (or methemoglobin), respectively. Only ferrohemoglobin (+2) can take up oxygen.

Hemoglobin is an allosteric protein. The binding of O₂ to a hemoglobin subunit induces conformational changes that are transmitted to other subunits, increasing their affinity for O₂. Therefore, the binding of oxygen to hemoglobin is said to be cooperative. In contrast, the binding of O₂ to myoglobin is not cooperative. This becomes evident when looking at the oxygen binding curves for both proteins, where saturation (Y) is the fraction of occupied oxygen binding sites and can range from 0 (when all sites are empty) to 1 (when all centers are busy); and pO₂ is the partial pressure of oxygen.