Prolyl endopeptidase

Prolyl endopeptidase (PE) also known as prolyl oligopeptidase or post-proline cleaving enzyme is an is_associated_with::enzyme that in humans is encoded by the PREP is_associated_with::gene.

Function
Prolyl endopeptidase is a large cytosolic is_associated_with::enzyme that belongs to a distinct class of is_associated_with::serine peptidases. It was first described in the cytosol of rabbit brain as an is_associated_with::oligopeptidase, which degrades the nonapeptide is_associated_with::bradykinin at the Pro-Phe bond. The enzyme is involved in the maturation and degradation of is_associated_with::peptide hormones and is_associated_with::neuropeptides such as is_associated_with::alpha-melanocyte-stimulating hormone, is_associated_with::luteinizing hormone-releasing hormone (LH-RH), is_associated_with::thyrotropin-releasing hormone, is_associated_with::angiotensin, is_associated_with::neurotensin, is_associated_with::oxytocin, is_associated_with::substance P and is_associated_with::vasopressin. PREP cleaves peptide bonds at the is_associated_with::C-terminal side of is_associated_with::proline residues. Its activity is confined to action on oligopeptides of less than 10 kD and it has an absolute requirement for the trans-configuration of the is_associated_with::peptide bond preceding proline.

Prolyl endopeptidases are involved in the maturation and degradation of peptide is_associated_with::hormones and is_associated_with::neuropeptides.

Structure
Prolyl endopeptidase is a cytosolic prolyl endopeptidase that cleaves is_associated_with::peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 is_associated_with::amino acids long. Only short protein residues are able to enter the active site of prolyl endopeptidase due to the distinct is_associated_with::beta-propeller region that acts as a gating filter mechanism.

Clinical significance
Altered PREP activity may be associated with is_associated_with::autism spectrum disorders and various psychological diseases such as is_associated_with::schizophrenia, is_associated_with::mania and is_associated_with::clinical depression.

However, there is conflicting information as to the exact role that prolyl endopeptidase plays in the pathophysiology of depression, with earlier studies documenting a decreased activity of the enzyme in depressed patients, but more recent studies demonstrating that inhibition of the same enzyme actually results in alleviation of depressive symptoms.

Some types of prolyl endopeptidase have been used in studies to decrease the propensity of is_associated_with::gluten-containing is_associated_with::wheat products to aggravate is_associated_with::coeliac disease. However, orally administered enzymes are potentially subject to inactivation in the gastrointestinal tract.

Inhibitors
Several prolyl endopeptidase inhibitors are known, and have been suggested as possible is_associated_with::nootropic and is_associated_with::antidepressant drugs. Notable compounds include


 * is_associated_with::Pramiracetam
 * is_associated_with::Baicalin
 * JTP-4819
 * KYP-2047
 * is_associated_with::S-17092
 * is_associated_with::Berberine