Prolyl isomerase

Prolyl Isomerase

Structure of a prolyl isomerase enzyme.

Prolyl isomerase is an enzyme that catalyzes the cis-trans isomerization of peptide bonds at proline residues in proteins. This isomerization is a critical step in protein folding and can affect the function and stability of proteins.

Function

Prolyl isomerases play a crucial role in the folding of proteins by accelerating the interconversion between the cis and trans isomers of proline peptide bonds. This isomerization is often a rate-limiting step in the folding of proteins, and prolyl isomerases help to overcome this barrier, ensuring proper protein conformation and function.

Types

There are several types of prolyl isomerases, including:

• Cyclophilins: A family of proteins that bind to the immunosuppressive drug cyclosporin A and have peptidyl-prolyl isomerase activity.
• FKBPs: Proteins that bind to the immunosuppressant drug FK506 and also exhibit prolyl isomerase activity.
• Parvulins: A family of prolyl isomerases that are distinct from cyclophilins and FKBPs.

Mechanism

Prolyl isomerases catalyze the isomerization of the peptide bond preceding a proline residue. This involves the rotation around the N-C_ bond of the proline, converting the bond from a cis to a trans configuration or vice versa. The enzyme stabilizes the transition state, lowering the activation energy required for the isomerization.

Biological Importance

Prolyl isomerases are involved in various cellular processes, including:

• Protein folding: Assisting in the proper folding of newly synthesized proteins.
• Signal transduction: Modulating the activity of signaling proteins by altering their conformation.
• Cell cycle regulation: Influencing the function of proteins involved in cell cycle progression.

Clinical Significance

Prolyl isomerases have been implicated in several diseases, including:

• Cancer: Dysregulation of prolyl isomerase activity can lead to aberrant protein folding and function, contributing to oncogenesis.
• Neurodegenerative diseases: Misfolded proteins are a hallmark of diseases such as Alzheimer's and Parkinson's, where prolyl isomerases may play a role.
• Immunosuppression: Cyclophilins and FKBPs are targets of immunosuppressive drugs, highlighting their importance in immune regulation.

Related Pages

• Protein folding
• Enzyme
• Peptide bond
• Proline