New insights on the catalytic center of proteins from peptidylprolyl isomerase group based on the FOD‐M model

Abstract

Generating the structure of the hydrophobic core is based on the orientation of hydrophobic residues towards the central part of the protein molecule with the simultaneous exposure of polar residues. Such a course of the protein folding process takes place with the active participation of the polar water environment. While the self‐assembly process leading to the formation of micelles concerns freely moving bi‐polar molecules, bipolar amino acids in polypeptide chain have limited mobility due to the covalent bonds. Therefore, proteins form a more or less perfect micelle‐like structure. The criterion is the hydrophobicity distribution, which to a greater or lesser extent reproduces the distribution expressed by the 3D Gaussian function on the protein body. The vast majority of proteins must ensure solubility, so a certain part of it—as it is expected—should reproduce the structuring of micelles. The biological activity of proteins is encoded in the part that does not reproduce the micelle‐like system. The location and quantitative assessment of the contribution of orderliness to disorder is of critical importance for the determination of biological activity. The form of maladjustment to the 3D Gauss function may be varied—hence the obtained high diversity of specific interactions with strictly defined molecules: ligands or substrates. The correctness of this interpretation was verified on the basis of the group of enzymes Peptidylprolyl isomerase—E.C.5.2.1.8. In proteins representing this class of enzymes, zones responsible for solubility—micelle‐like hydrophobicity system—the location and specificity of the incompatible part in which the specific activity of the enzyme is located and coded were identified. The present study showed that the enzymes of the discussed group show two different schemes of the structure of catalytic center (taking into account the status as defined by the fuzzy oil drop model).

External Force Field for Protein Folding in Chaperonins─Potential Application in In Silico Protein Folding

“…The elimination of a few residues produces significant differences in the level of O i toward T i and helps identify that part of the protein where the hydrophobicity pattern is micelle-like. These eliminated residues (with a local deficit in hydrophobicity due to the frequently present cavity) are generally residues that constitute the active center . The local superficial excess of hydrophobicity is often used for the complexation of another chain with a similar hydrophobicity exposure .…”

“…These eliminated residues (with a local deficit in hydrophobicity due to the frequently present cavity) are generally residues that constitute the active center. 39 The local superficial excess of hydrophobicity is often used for the complexation of another chain with a similar hydrophobicity exposure. 23 The amphipathic membrane environment requires a hydrophobicity ordering that opposes the micelle-like ordering.…”

Hydrophobicity-Based Force Field In Enzymes

“…Treating all mentioned methods together with the model proposed in this paper may deliver an effective tool for the de novo design of enzymes of expected, defined activity. 86 …”

Probing the functional hotspots inside protein hydrophobic pockets by in situ photochemical trifluoromethylation and mass spectrometry

“…Next, the reaction solution with H 2 O 18 was applied to determine the oxygen source of photo-oxidation. 46 Interestingly, the monooxidation product was still dominated with 16 O (from dissolved O 2 ), while both 16 O and 18 O were incorporated into the multipleoxidation forms of products (Fig. S11B †).…”

“…Hydrophobic interaction is essential during protein folding into an ordered structure with a hydrophilic surface and hydrophobic core. 11,12 Further, the protein recognition of small molecules such as drugs, 13,14 ligand binding with receptors, 15 and enzyme biocatalysis reactions 16,17 oen occur in protein hydrophobic pockets with essential functional hotspots. Recently, studies of structural biology have reported the key binding sites in the hydrophobic pockets of membrane proteins, such as vitamin K epoxide reductases (VKOR) with vitamin K antagonists, 18 ATP-binding cassette (ABD) transporters with inhibitors, 19 and G-protein-coupled receptors (GPCRs) with various ligands.…”