PREP | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | PREP, PE, PEP, prolyl endopeptidase | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 600400; MGI: 1270863; HomoloGene: 2042; GeneCards: PREP; OMA:PREP - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Prolyl endopeptidase (PE) also known as prolyl oligopeptidaseorpost-proline cleaving enzyme is an enzyme that in humans is encoded by the PREP gene.[4][5]
prolyl oligopeptidase | |||||||||
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Identifiers | |||||||||
EC no. | 3.4.21.26 | ||||||||
CAS no. | 72162-84-6 | ||||||||
Databases | |||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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Prolyl endopeptidase is a large cytosolic enzyme that belongs to a distinct class of serine peptidases. It was first described in the cytosol of rabbit brain as an oligopeptidase, which degrades the nonapeptide bradykinin at the Pro-Phe bond.[6] The enzyme is involved in the maturation and degradation of peptide hormones and neuropeptides such as alpha-melanocyte-stimulating hormone, luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone, angiotensin, neurotensin, oxytocin, substance P and vasopressin. PREP cleaves peptide bonds at the C-terminal side of 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 peptide bond preceding proline.
Prolyl endopeptidases are involved in the maturation and degradation of peptide hormones and neuropeptides.[5]
Prolyl endopeptidase is a cytosolic prolyl endopeptidase that cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long. Only short protein residues are able to enter the active site of prolyl endopeptidase due to the distinct beta-propeller region that acts as a gating filter mechanism.[7][8]
Prolyl endopeptidase was also found to be involved in the metabolism of VHL-PROTACs in in vitro studies.[9]
Altered PREP activity may be associated with autism spectrum disorders and various psychological diseases such as schizophrenia, mania and clinical depression.[10]
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.[11][12]
Some types of prolyl endopeptidase have been used in studies to decrease the propensity of gluten-containing wheat products to aggravate coeliac disease.[13] However, orally administered enzymes are potentially subject to inactivation in the gastrointestinal tract.[14]
Several prolyl endopeptidase inhibitors are known,[15][16] and have been suggested as possible nootropic and antidepressant drugs.[17][18] Notable compounds include:
PDB gallery
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1e5t: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, MUTANT
1e8m: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, MUTANT, COMPLEXED WITH INHIBITOR
1e8n: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, MUTANT, COMPLEXED WITH PEPTIDE
1h2w: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN
1h2x: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, Y473F MUTANT
1h2y: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, Y473F MUTANT WITH COVALENTLY BOUND INHIBITOR Z-PRO-PROLINAL
1h2z: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, S554A MUTANT WITH BOUND PEPTIDE LIGAND SUC-GLY-PRO
1o6f: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, D641A MUTANT WITH BOUND PEPTIDE LIGAND SUC-GLY-PRO
1o6g: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, D641N MUTANT WITH BOUND PEPTIDE LIGAND SUC-GLY-PRO
1qfm: PROLYL OLIGOPEPTIDASE FROM PORCINE MUSCLE
1qfs: PROLYL OLIGOPEPTIDASE FROM PORCINE MUSCLE WITH COVALENTLY BOUND INHIBITOR Z-PRO-PROLINAL
1uoo: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, S554A MUTANT WITH BOUND PEPTIDE LIGAND GLY-PHE-ARG-PRO
1uop: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, S554A MUTANT WITH BOUND PEPTIDE LIGAND GLY-PHE-GLU-PRO
1uoq: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, S554A MUTANT WITH BOUND PEPTIDE LIGAND GLU-PHE-SER-PRO
1vz2: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, Y73C/V427C/C255T MUTANT
1vz3: PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, T597C MUTANT
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