Prolyl isomerase: Difference between revisions

Latest revision as of 11:34, 15 February 2025

Prolyl Isomerase[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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-'''Prolyl isomerase''' is an enzyme that catalyzes the cis-trans isomerization of proline imidic peptide bonds in proteins, which is a critical process in protein folding and conformational changes in both physiological and pathological conditions. This enzyme plays a significant role in various cellular processes, including signal transduction, cell cycle regulation, and protein trafficking. Prolyl isomerases are found in all eukaryotes, as well as in bacteria and archaea, highlighting their essential function in cellular biology.
+== Prolyl Isomerase ==
+[[File:PDB_1nmw_EBI.jpg|thumb|right|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 isomerase facilitates the interconversion between the cis and trans isomers of the peptide bond preceding a proline residue within polypeptides. This isomerization is a rate-limiting step in many protein folding processes because the rotation around the peptide bond is energetically unfavorable due to the unique cyclic structure of proline. By catalyzing this reaction, prolyl isomerases play a crucial role in ensuring proteins fold into their correct three-dimensional structures, which is essential for their biological function.
-== Classification ==
+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.
-Prolyl isomerases are classified into three major families based on their structural and functional characteristics:
-* [[Cyclophilin]]s (CYPs)
+== Types ==
-* [[FK506-binding proteins]] (FKBPs), also known as tacrolimus binding proteins
-* [[Parvulins]]
-Each family exhibits distinct substrate specificities, cellular localizations, and biological functions. Cyclophilins and FKBPs are also known for their role in immunosuppression, as they are the target of the immunosuppressive drugs cyclosporin A and FK506 (tacrolimus), respectively.
+There are several types of prolyl isomerases, including:
-== Biological Significance ==
+* '''[[Cyclophilin]]s''': A family of proteins that bind to the immunosuppressive drug cyclosporin A and have peptidyl-prolyl isomerase activity.
-Prolyl isomerases are involved in numerous cellular processes beyond protein folding. They participate in the regulation of transcription, cell cycle progression, and apoptosis. For example, the interaction between prolyl isomerases and certain transcription factors can influence the transcription of genes involved in cell growth and differentiation. Additionally, some prolyl isomerases have been implicated in the pathogenesis of diseases, including cancer, neurodegenerative diseases, and infectious diseases, making them potential targets for therapeutic intervention.
+* '''[[FK506-binding protein|FKBP]]s''': Proteins that bind to the immunosuppressant drug FK506 and also exhibit prolyl isomerase activity.
+* '''[[Parvulin]]s''': A family of prolyl isomerases that are distinct from cyclophilins and FKBPs.
-== Research and Therapeutic Applications ==
+== Mechanism ==
-Given their involvement in a wide range of biological processes and diseases, prolyl isomerases have been the focus of extensive research aimed at understanding their mechanism of action and exploring their potential as therapeutic targets. Inhibitors of prolyl isomerases, such as cyclosporin A for cyclophilins and FK506 for FKBPs, have been successfully used as immunosuppressive agents in organ transplantation. Ongoing research is aimed at developing new drugs targeting prolyl isomerases for the treatment of various diseases, including cancer, Alzheimer's disease, and viral infections.
+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 ==
-== See Also ==
 * [[Protein folding]]
-* [[Immunosuppression]]
+* [[Enzyme]]
-* [[Cyclosporin A]]
+* [[Peptide bond]]
-* [[FK506]]
+* [[Proline]]
-== References ==
-{{Reflist}}
 [[Category:Enzymes]]
 [[Category:Protein folding]]
-[[Category:Cell biology]]
-{{medicine-stub}}