Question

how does guanidine unfold myoglobin? what type of molecular interaction does it interrupt?

Answer 1

Before I discuss the role of guanidine in the denaturation of proteins I would like to discuss a little about what is the nature of guanidine.

Guanidines are organic compounds that share a common functional group with a general structure of (R1R2N)(R3R4N)C=N?R5. The central bond being the imine within this group. The structure of guanidine is as follows

UNFOLDING OF MYOGLOBIN BY GUANIDINE

Unfolding of proteins is assumed to occur in two ways. It includes the process where the denaturants where protein – protein interactions (hydrophobic/hydrophilic) weaken. It is considered that the proteins damage extensively as the hydrogen bonds of water around the protein are ruptured.

Guanidinium chloride is the most common denaturant that is used for protein unfolding. Mechanism of unfolding of protein proceeds through the disruption of hydrophobic interactions. Guanidine does not make any hydrogen bonds with the protein but it disrupts the hydrophobic interactions within the native state of protein, specifically between the aromatic chains. 6-8M concentrations of guanidine is enough to denature any protein. The denaturation results in the formation of completely random polymers diffusing freely.

The denaturation of Myoglobin protein by the guanidine involves at least a molecular intermediate which is observed at low denaturant conditions. The molecular properties of the intermediate usually resembles the acid-denatured form of the protein. It is often considered a simple process of two steps. A hypothesis explains that the molecular intermediated formed usually lose the ability to bind to the heme but they are still retained as structurally organised and the disarrangement of heme binding sites occurred due to unfolding of one of the two protein domainsin the myoglobin molecule. The peptide bonds of the protein are hydrophilic so they attract water molecules and the hydrophobic portion of the water molecules also gets exposed leading to association of proteins by their hydrophobic regions so that random three dimensional structures are formed thus forming random coiled structures.

MOLECULAR INTERACTION INTERRUPTED

Hydrophobic and hydrophilic interactions within the protein is disrupted by the use of guanidine.