Role of Disulfide Bonds in Stabilizing the Conformation of Selected Enzymes—An Approach Based on Divergence Entropy Applied to the Structure of Hydrophobic Core in Proteins

Mateusz Banach,Irena Roterman,Barbara Kalinowska,Leszek Konieczny

doi:10.3390/e18030067

Abstract

One of the factors responsible for tertiary structural stabilization in proteins is the presence of the hydrophobic core—a result of hydrophobic interactions within the protein body. In some proteins (especially extracellular ones) additional stabilization is provided by covalent bonds between selected Cys residues, commonly referred to as disulfide bonds. The mutual interplay of both factors and their respective contributions to stabilization are the focus of this work. The assessment of the effects of disulfide bonds isinterpreted by Fuzzy Oil Drop (FOD) model in which individual polypeptide chain fragments (including fragments which participate in SS bonds) can be evaluated in the context of their influence upon tertiary structural stabilization by comparing their corresponding theoretical and idealized hydrophobicity density distributions. The proteins were identified with both factors reinforcing each other, as well as proteins where they seem to counteract each other. The analysis presents a number of enzymes, including ribonuclease, lysozyme, disulfide isomerase and phospholipase.

Highlights

The folding process—the process by which a protein adopts a conformation which supports biological activity—is primarily driven by optimization of non-binding interactions
Our aim was to determine the degree to which a given structure is stabilized by SS bonds and assess the involvement of a well ordered hydrophobic core in structural stabilization
In order to enable comparative analysis we focused on the observed hydrophobicity density (Oi ), since this parameter determines the overall status of the residue and is affected by interactions with neighboring residues (9 Å radius)

Summary

Introduction

The folding process—the process by which a protein adopts a conformation which supports biological activity—is primarily driven by optimization of non-binding interactions. In some proteins ( extracellular ones) covalent bonds between Cys residues, i.e., disulfide bonds, must be taken into account. The main purpose of such bonds is structural stabilization. Hydrophobic interactions, resulting in the emergence of the hydrophobic core, tend to exert a stabilizing influence upon tertiary protein structure. The stabilizing role of disulfide bonds is well known [1,2]. Formation of structures which include disulfide bonds is significantly more complicated than in the case of polypeptide chains where such bonds are absent. From a chemical point of view, the former case calls for additional redox reactions

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Conclusion