BIOCHEMISTRY - Textbook - Ostapchenko, L. I. - 2012

Chapter 5. STRUCTURE, PROPERTIES, AND FUNCTIONS OF PROTEINS

5.5. Functional Characteristics of Oligomeric Proteins

5.5.1. Structure and Functions of Myoglobin

Myoglobin is classified as a heme-containing protein, meaning it incorporates a prosthetic group (heme) tightly bound to the protein moiety. Being a globular protein, myoglobin consists of a single polypeptide chain.

Myoglobin is predominantly found in red Muscles, where it acts as an oxygen storage reserve. During intense muscular activity, when tissue partial pressure of oxygen drops, O₂ dissociates from the myoglobin complex and is utilized in cellular Cell/35.html">Mitochondria to generate the energy required for Muscle contraction. Myoglobin comprises a non-protein component (heme) and a protein component (apomyoglobin).

Heme is a cyclic tetrapyrrole molecule in which four pyrrole rings are linked by methene bridges and bear four methyl, two vinyl, and two propionate side chains. This organic moiety of heme is known as protoporphyrin. While 15 different side-chain arrangements are theoretically possible, only a single isomer—protoporphyrin IX—is found in Hemoproteins. In the heme molecule, the four nitrogen atoms of the pyrrole rings are coordinated with an Fe²⁺ ion situated at the center of the molecule (Fig. 5.29).

Apomyoglobin is the protein portion of myoglobin; its Primary Structure consists of a sequence of 153 Amino Acids folded into eight α-helices in the Secondary structure. The α-helices are designated by Latin letters from A to H, starting from the N-terminus of the polypeptide chain, and contain between 7 and 23 amino acids each. Individual amino acids in the Introduction/19.html">Primary structure of apomyoglobin are denoted either by their ordinal position from the N-terminus (e.g., His₆₄, Phe₁₃₈) or by the letter of the corresponding α-Helix followed by the residue's position within that helix starting from the N-terminus (e.g., His F₈).

The tertiary structure forms a compact globule with virtually no empty space inside, stabilized by loops and turns in the non-helical Regions of the protein. The interior of the molecule is almost entirely composed of hydrophobic residues, with the exception of two Histidine residues located in the Active Site.

Heme acts as a specific Ligand for apomyoglobin, binding to the protein moiety within a crevice nestled between two α-helices, F and E. The heme-binding pocket is formed predominantly by hydrophobic amino acid residues that surround the hydrophobic pyrrole rings of the heme.

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Fig. 5.29. Structure of heme found in Myoglobin and Hemoglobin

In addition to hydrophobic amino acids, the Active Site of apomyoglobin includes two histidine residues (His₆₄ and His₉₃, or His E₇ and His F₈), which play a crucial role in protein function. They are positioned on opposite sides of the heme plane and belong to the F and E helices, between which the heme is lodged. The iron atom in heme can form six coordination bonds: four hold Fe²⁺ within the protoporphyrin IX ring system (by coordinating with the nitrogen atoms of the pyrrole rings), and the fifth bond forms between Fe²⁺ and the nitrogen atom of the imidazole ring of His F₈ (Fig. 5.30).

Fig. 5.30. Arrangement of heme in the active site of apomyoglobin and apomyoglobin protomers

Although His E₇ is not directly bonded to the heme iron, it is nevertheless essential for the proper orientation and binding of the second ligand, O₂, to myoglobin.

The amino acid microenvironment of the heme provides optimal conditions for the tight yet Reversible Binding of O₂ to the Fe²⁺ of myoglobin. The surrounding hydrophobic amino acid residues prevent Water molecules from entering the myoglobin binding pocket and inhibit The oxidation of Fe²⁺ to Fe³⁺. Ferric iron (Fe³⁺) within the heme is incapable of binding O₂.