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

Abstract

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.

Sequence-to-Structure Relation in Proteins-Amyloidogenic Proteins with Chameleon Sequences

“…Fragments delimited by SS bonds are accordant, which suggests that the hydrophobic core may play a role in guiding Cys residues towards their intended locations and ensuring the formation of disulfide bonds. This is in contrast to another frequently observed phenomenon, where SS-bonds introduce structural deformations which counteract hydrophobic effects and thereby stabilize the molecule in a specific locally unstable tertiary conformation [34].…”

“…Subsets of proteins listed in Gendoo and Harrison [31] have been subjected to analysis which focused on the stabilizing effects of an ordered hydrophobic core [32][33][34]. Assuming that the core is a major contributor to tertiary stabilization, we can attempt to determine its role in situations where the protein undergoes major structural rearrangement.…”

Influence of the Aqueous Environment on Protein Structure—A Plausible Hypothesis Concerning the Mechanism of Amyloidogenesis

“…Generation of a highly specific enzymatically active site requires certain distortions in the hydrophobic force field, as described in [12,61]. This process also calls for a suitable carrier of information which must be contributed by the protein's environment.…”

“…The fuzzy oil drop (FOD) model is a modification of the previously described oil drop model which asserts that hydrophobic residues tend to migrate to the center of the protein body while hydrophilic residues are exposed on its surface [11,12]. A visual description of this model is presented in Figure 1A where the dark area corresponds to a highly hydrophobic "core" while light areas represent the hydrophilic "shell".…”

“…In our study, however, the object of analysis is not a sequence of characters (amino acid codes) but rather the distribution of hydrophobicity along the input chain. The intrinsic hydrophobicity scale proposed in [12] is taken as the basis for computing correlation coefficients. Correlation is calculated for the intrinsic hydrophobicity (as embodied by a particular fragment) and for the observed (O) as well as theoretical (T) distributions.…”