protein peptidyl-prolyl isomerization

Definition

Target type: biologicalprocess

The modification of a protein by cis-trans isomerization of a proline residue. [GOC:krc, PMID:16959570]

Protein peptidyl-prolyl isomerization is a crucial step in protein folding and function, catalyzed by peptidyl-prolyl isomerases (PPIases). This process involves the cis-trans isomerization of the peptide bond preceding proline residues, which are known for their rigid structure due to the cyclic nature of their side chain.

In its native state, proline residues often adopt the trans conformation, where the carbonyl group of the preceding residue and the nitrogen atom of the proline residue are on opposite sides of the peptide bond. However, in certain protein structures, the cis conformation, where these groups are on the same side, is required for proper folding and function.

PPIases accelerate the rate of this isomerization reaction, which can be extremely slow in the absence of an enzyme. There are two main classes of PPIases: cyclophilins, FK506-binding proteins (FKBPs), and parvulin.

The mechanism of action involves the PPIase binding to the peptide bond preceding proline, bringing the substrate into close proximity with the active site. The active site contains a conserved catalytic residue, usually a proline or a tyrosine, which interacts with the peptide bond and facilitates the isomerization.

The process is highly specific for proline residues due to the unique properties of their side chain. The cyclic structure of proline restricts the rotation around the peptide bond, leading to the formation of cis and trans conformations with distinct energetic states.

PPIases play essential roles in various cellular processes, including protein folding, signal transduction, and immune response. Defects in PPIases can contribute to various diseases, such as cancer, neurodegenerative disorders, and autoimmune diseases.

The precise role of PPIases in protein folding varies depending on the protein in question. Some proteins require cis-proline residues for proper folding, while others rely on the trans conformation. PPIases ensure that these proline residues are in the correct conformation for proper protein structure and function.'
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Proteins (10)

Compounds (33)