Structure and Function of Globular Hemeproteins: Myoglobin and Hemoglobin

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Globular Hemeproteins

Overview of Globular Proteins

Globular proteins are compact, generally spherical ("globelike") proteins that are somewhat water-soluble. Their structure and solubility are determined by the distribution of hydrophilic and hydrophobic amino acids.

Hydrophilic amino acids are typically found on the outer surface, interacting with the aqueous environment.
Hydrophobic (nonpolar) amino acids are buried in the protein's interior, stabilized by hydrophobic interactions.
These interactions help maintain the protein's globular structure and function.
Clinically important examples include hemoglobin and myoglobin.

Hemeproteins

Hemeproteins are a class of globular proteins that contain a heme prosthetic group, which is essential for their biological function.

The heme group is a planar, cyclic structure (porphyrin ring) with a central iron ion (Fe2+).
The protein's three-dimensional structure dictates the orientation and function of the heme group.
Heme allows for rapid and reversible electron transfer (as in cytochromes) or oxygen binding (as in myoglobin and hemoglobin).
In enzymes like catalase, the heme group is involved in the breakdown of hydrogen peroxide.
Structural changes in the protein can affect the alignment of the iron atom, influencing binding affinity and function.

Structure of the Heme Group

The heme group is a prosthetic group essential for oxygen binding and electron transfer in hemeproteins.

Composed of a porphyrin ring with a central Fe2+ ion coordinated to four nitrogen atoms.
The iron atom can form two additional bonds perpendicular to the plane of the ring:
- One bond is typically to a histidine residue of the protein (proximal histidine).
- The other bond is available for binding oxygen (O2).

Myoglobin

Structure and Function

Myoglobin is an oxygen-binding protein found primarily in heart and skeletal muscle. It serves as an oxygen reservoir and facilitates oxygen transport within muscle cells.

Consists of a single polypeptide chain (~153 amino acids).
Structurally similar to the individual subunits of hemoglobin.
Contains one heme group and can bind one molecule of O2.

Structural Features

Compact structure: ~80% of the polypeptide is folded into eight α-helices (labeled A–H).
Hydrophobic core: Nonpolar amino acids are packed inside, stabilized by hydrophobic interactions.
Hydrophilic surface: Polar amino acids are mostly on the surface, forming hydrogen bonds with water or other residues.

Heme Group in Myoglobin

The heme group is located in a crevice lined with nonpolar amino acids.
Two histidine residues are critical:
- Proximal histidine (F8): Directly binds the Fe2+ of heme.
- Distal histidine (E7): Does not bind iron directly but stabilizes the binding of O2 to Fe2+.
This arrangement creates a microenvironment that facilitates reversible oxygen binding and prevents oxidation of Fe2+ to Fe3+.

Hemoglobin

Structure and Function

Hemoglobin is the major oxygen-transport protein in red blood cells (RBCs), delivering O2 from the lungs to tissues and facilitating CO2 and H+ transport back to the lungs.

Adult hemoglobin (HbA) is a tetramer: two α and two β polypeptide chains (α2β2).
Each subunit contains a heme group, allowing one hemoglobin molecule to bind up to four O2 molecules.
Subunits are held together by noncovalent interactions (hydrophobic, ionic, and hydrogen bonds).
Hemoglobin can also transport protons (H+) and CO2.
Oxygen-binding properties are regulated by allosteric effectors (e.g., pH, CO2, 2,3-BPG).

Comparison of Myoglobin and Hemoglobin

Property	Myoglobin	Hemoglobin
Location	Muscle tissue	Red blood cells
Subunit structure	Monomer (1 polypeptide)	Tetramer (2 α, 2 β chains)
Heme groups per molecule	1	4
O2 binding sites per molecule	1	4
Function	O2 storage and diffusion in muscle	O2 transport in blood

Key Terms

Globular protein: A protein with a compact, spherical shape, generally soluble in water.
Heme: An iron-containing prosthetic group essential for oxygen binding.
Proximal histidine (F8): The histidine residue directly bonded to the heme iron.
Distal histidine (E7): The histidine residue that stabilizes O2 binding to the heme iron.

Example: Oxygen Binding

Myoglobin binds O2 with high affinity, facilitating O2 storage in muscle.
Hemoglobin's quaternary structure allows cooperative binding, enabling efficient O2 uptake in the lungs and release in tissues.

Additional info: The cooperative binding of O2 by hemoglobin is a classic example of allosteric regulation, which is not observed in myoglobin due to its monomeric structure.