Prolyl Endopeptidase

spinqualitylabelsall models Prolyl endopeptidase of Sphingomonas capsulata at 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Prolyl endopeptidases (PEPs) are a class of serine proteases which cleave peptide bonds on the c-terminal side of internal proline residues.

StructureStructure

FunctionFunction

PEPs are thought to have a role in the degradation of neuropeptides due to the high concentration of PEPs in the brain and the fact that PEPs have been shown to degrade several neuropeptides(vasopressin, β-endorphin, thyroliberin). The distribution of PEP in the brain has been found to be similar to that of certain receptors of neuropeptides which supports PEPs being involved in the degradation of neuropeptide transmitters.

Binding MechanismBinding Mechanism

Catalytic( and β-propeller domains(

Pharmaceutical PossibilitiesPharmaceutical Possibilities

Both human and microbial PEP have been the focus of research into their viability as therapeutic agents for several diseases. The ability of PEPs to cleave internal proline peptide bonds is of interest in the treatment of Celiac Disease which is caused by a reaction to gluten, a proline rich protein found in wheat and wheat subspecies. CITE BESEDIN PEPs have also been linked to several neurological disorders due to high activity in the brain and proposed role in the degradation of neuropeptides.

Celiac DiseaseCeliac Disease

Celiac Disease(CD) is a genetic disorder marked by diarrhea, fatigue, weight loss, and villous atrophy due to the consumption of certain proteins such as gluten and other prolamins found in wheat and wheat subspecies. The symptoms of CD are due to an auto-immune inflammatory reaction that occurs in the small intestine due to prolamins that are rich in proline residues and known to be resistant to many proteases.

There is currently no cure for Celiac Disease and the main treatment is to simply avoid eating prolamin containing foods.

Prolyl endopeptidases are a promising therapeutic agent due to their ability to degrade the protein rich prolamins and inhibit the inflammatory reaction. An early idea for treatment is to orally administer certain microbial PEPs which could directly degrade prolamins in the intestine and reduce the auto-immune response. The key for this possibility is to be able to protect the PEPs from being degraded by gastric acids while allowing them to be able to be functional in the small intestine once the acidity is decreased.