Prolyl endopeptidase
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Prolyl endopeptidase
| Prolyl endopeptidase | |||||||||||||
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 Prolyl oligopeptidase from porcine brain. PDB rendering based on 1e5t[1]. |
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| Identifiers | |||||||||||||
| Symbols | PREP; PE; PEP | ||||||||||||
| External IDs | OMIM: 600400 MGI: 1270863 HomoloGene: 2042 ChEMBL: 3202 GeneCards: PREP Gene | ||||||||||||
| EC number | 3.4.21.26 | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 5550 | 19072 | |||||||||||
| Ensembl | ENSG00000085377 | ENSMUSG00000019849 | |||||||||||
| UniProt | P48147 | Q9QUR6 | |||||||||||
| RefSeq (mRNA) | NM_002726.4 | NM_011156.2 | |||||||||||
| RefSeq (protein) | NP_002717.3 | NP_035286.1 | |||||||||||
| Location (UCSC) | Chr 6: 105.73 – 105.85 Mb |
Chr 10: 44.79 – 44.88 Mb |
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| PubMed search | [2] | [3] | |||||||||||
| prolyl oligopeptidase | |||||||
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| Identifiers | |||||||
| EC number | 3.4.21.26 | ||||||
| CAS number | 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 / EGO | ||||||
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Prolyl endopeptidase (PREP) or prolyl oligopeptidase, sometimes post-proline cleaving enzyme) 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.[2] 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.
Some types of prolyl endopeptidase have been used in studies to decrease the propensity of gluten-containing wheat products to aggravate coeliac disease.[3] However, orally administered enzymes are potentially subject to inactivation in the gastrointestinal tract.[4]
In humans prolyl endopeptidase] is encoded by the PREP gene.[5][6] The protein encoded by this gene 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 endopeptidases have been reported to be involved in the maturation and degradation of peptide hormones and neuropeptides.[6] There's an indication that altered PREP activity is associated with autism spectrum disorders and various psychological diseases such as schizophrenia, mania and clinical depression.[9]
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Contents
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Inhibitors
Several prolyl endopeptidase inhibitors are known,[10][11] and have been suggested as possible nootropic and antidepressant drugs.[12][13] Notable compounds include
References
- ^ Fulop, V.; Szeltner, Z.; Polgár, L. (2000). "Catalysis of serine oligopeptidases is controlled by a gating filter mechanism". EMBO Reports 1 (3): 277–281. doi:10.1093/embo-reports/kvd048. PMC 1083722. PMID 11256612. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1083722.
- ^ Oliveira EB, Martins AR, Camargo ACM (May 1976). "Isolation of brain endopeptidases: Influence of size and sequence of substrates structurally related to bradykinin". Biochemistry 15 (9): 1967–74. doi:10.1021/bi00654a026. PMID 5120.
- ^ Stepniak D, Spaenij-Dekking L, Mitea C, et al. (Oct 2006). "Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease". Am J Physiol Gastrointest Liver Physiol 291 (4): G621–9. doi:10.1152/ajpgi.00034.2006. PMID 16690904.
- ^ Fuhrmann G, Leroux JC (2011) In vivo fluorescence imaging of exogenous enzyme activity in the gastrointestinal tract. Proceedings of the National Academy of Sciences, 108, 9032-9037 [1]
- ^ Vanhoof G, Goossens F, Hendriks L, De Meester I, Hendriks D, Vriend G, Van Broeckhoven C, Scharpe S (Dec 1994). "Cloning and sequence analysis of the gene encoding human lymphocyte prolyl endopeptidase". Gene 149 (2): 363–6. doi:10.1016/0378-1119(94)90177-5. PMID 7959018.
- ^ a b "Entrez Gene: PREP prolyl endopeptidase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5550.
- ^ V. Fulop, Z. Bocskei, L. Polgar (1998). "Prolyl Oligopeptidase: An Unusual b-Propeller Domain Regulates Proteolysis". Cell 94: 161. http://ac.els-cdn.com/S0092867400814166/1-s2.0-S0092867400814166-main.pdf?_tid=34c234b2473fd5aef9b0fb87faa3111d&acdnat=1336601668_816a9e212f80d61785a0f7ff460d982b.
- ^ V. Fulop, Z. Szeltner, L. Polgar (2000). "Catalysis of serine oligopeptidases is controlled by a gating filter mechanism". EMBO Rep. 1: 277. http://www.nature.com.ezp2.lib.umn.edu/embor/journal/v1/n3/full/embor589.html.
- ^ Momeni N, Nordström BM, Horstmann V, Avarseji H, Sivberg BV (2005). "Alterations of prolyl endopeptidase activity in the plasma of children with autistic spectrum disorders". BMC Psychiatry 5: 27. doi:10.1186/1471-244X-5-27. PMC 1190193. PMID 15932649. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1190193.
- ^ Jarho EM, Venäläinen JI, Poutiainen S, et al. (March 2007). "2(S)-(Cycloalk-1-enecarbonyl)-1-(4-phenyl-butanoyl)pyrrolidines and 2(S)-(aroyl)-1-(4-phenylbutanoyl)pyrrolidines as prolyl oligopeptidase inhibitors". Bioorg. Med. Chem. 15 (5): 2024–31. doi:10.1016/j.bmc.2006.12.036. PMID 17215128.
- ^ Kánai K, Arányi P, Böcskei Z, et al. (December 2008). "Prolyl oligopeptidase inhibition by N-acyl-pro-pyrrolidine-type molecules". J. Med. Chem. 51 (23): 7514–22. doi:10.1021/jm800944x. PMID 19006380.
- ^ Morain P, Boeijinga PH, Demazières A, De Nanteuil G, Luthringer R (2007). "Psychotropic profile of S 17092, a prolyl endopeptidase inhibitor, using quantitative EEG in young healthy volunteers". Neuropsychobiology 55 (3-4): 176–83. doi:10.1159/000107070. PMID 17700042.
- ^ Khlebnikova NN, Krupina NA, Bogdanova NG, Zolotov NN, Kryzhanovskii GN (January 2009). "Effects of prolylendopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine on experimental depressive syndrome development in rats". Bull. Exp. Biol. Med. 147 (1): 26–30. PMID 19526123.
- ^ Tarragó T, Kichik N, Claasen B, Prades R, Teixidó M, Giralt E (August 2008). "Baicalin, a prodrug able to reach the CNS, is a prolyl oligopeptidase inhibitor". Bioorg. Med. Chem. 16 (15): 7516–24. doi:10.1016/j.bmc.2008.04.067. PMID 18650094.
- ^ Toide K, Shinoda M, Miyazaki A (1998). "A novel prolyl endopeptidase inhibitor, JTP-4819--its behavioral and neurochemical properties for the treatment of Alzheimer's disease". Rev Neurosci 9 (1): 17–29. PMID 9683325.
- ^ Jalkanen AJ, Puttonen KA, Venäläinen JI, Sinervä V, Mannila A, Ruotsalainen S, Jarho EM, Wallén EA, Männistö PT (February 2007). "Beneficial effect of prolyl oligopeptidase inhibition on spatial memory in young but not in old scopolamine-treated rats". Basic Clin. Pharmacol. Toxicol. 100 (2): 132–8. doi:10.1111/j.1742-7843.2006.00021.x. PMID 17244263.
- ^ Morain P, Lestage P, De Nanteuil G, Jochemsen R, Robin JL, Guez D, Boyer PA (2002). "S 17092: a prolyl endopeptidase inhibitor as a potential therapeutic drug for memory impairment. Preclinical and clinical studies". CNS Drug Rev 8 (1): 31–52. PMID 12070525.
Further reading
- Mentlein R (1988). "Proline residues in the maturation and degradation of peptide hormones and neuropeptides.". FEBS Lett. 234 (2): 251–6. doi:10.1016/0014-5793(88)80092-9. PMID 3292288.
- Wilk S (1984). "Prolyl endopeptidase.". Life Sci. 33 (22): 2149–57. doi:10.1016/0024-3205(83)90285-0. PMID 6358755.
- Koida M, Walter R (1977). "Post-proline cleaving enzyme. Purification of this endopeptidase by affinity chromatography.". J. Biol. Chem. 251 (23): 7593–9. PMID 12173.
- Swanson AA, Davis RM, Meinhardt NC (1985). "Proteases in human lenses and their possible significance.". Curr. Eye Res. 4 (1): 43–8. doi:10.3109/02713688508999965. PMID 2858361.
- Momand J, Clarke S (1988). "Rapid degradation of D- and L-succinimide-containing peptides by a post-proline endopeptidase from human erythrocytes.". Biochemistry 26 (24): 7798–805. doi:10.1021/bi00398a040. PMID 3480758.
- Checler F, Vincent JP, Kitabgi P (1986). "Purification and characterization of a novel neurotensin-degrading peptidase from rat brain synaptic membranes.". J. Biol. Chem. 261 (24): 11274–81. PMID 3525564.
- Daly DJ, Maskrey P, Pennington RJ (1985). "Characterization of proline endopeptidase from skeletal muscle.". Int. J. Biochem. 17 (4): 521–4. doi:10.1016/0020-711X(85)90149-1. PMID 3891453.
- Sumi S, Mizutani S, Narita O, Tomoda Y (1985). "Purification and properties of a human placental post-proline endopeptidase.". Nippon Sanka Fujinka Gakkai Zasshi 36 (10): 1943–51. PMID 6389730.
- Goossens F, De Meester I, Vanhoof G, et al. (1995). "The purification, characterization and analysis of primary and secondary-structure of prolyl oligopeptidase from human lymphocytes. Evidence that the enzyme belongs to the alpha/beta hydrolase fold family.". Eur. J. Biochem. 233 (2): 432–41. doi:10.1111/j.1432-1033.1995.432_2.x. PMID 7588785.
- Shirasawa Y, Osawa T, Hirashima A (1994). "Molecular cloning and characterization of prolyl endopeptidase from human T cells.". J. Biochem. 115 (4): 724–9. PMID 8089089.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Goossens FJ, Wauters JG, Vanhoof GC, et al. (1996). "Subregional mapping of the human lymphocyte prolyl oligopeptidase gene (PREP) to human chromosome 6q22.". Cytogenet. Cell Genet. 74 (1-2): 99–101. doi:10.1159/000134391. PMID 8893811.
- Fülöp V, Böcskei Z, Polgár L (1998). "Prolyl oligopeptidase: an unusual beta-propeller domain regulates proteolysis.". Cell 94 (2): 161–70. doi:10.1016/S0092-8674(00)81416-6. PMID 9695945.
- Quinto BM, Juliano MA, Hirata I, et al. (2001). "Characterization of a prolyl endopeptidase (kininase) from human urine using fluorogenic quenched substrates.". Int. J. Biochem. Cell Biol. 32 (11-12): 1161–72. doi:10.1016/S1357-2725(00)00060-1. PMID 11137456.
- Irazusta J, Larrinaga G, González-Maeso J, et al. (2002). "Distribution of prolyl endopeptidase activities in rat and human brain.". Neurochem. Int. 40 (4): 337–45. doi:10.1016/S0197-0186(01)00078-X. PMID 11792464.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Bellemère G, Morain P, Vaudry H, Jégou S (2003). "Effect of S 17092, a novel prolyl endopeptidase inhibitor, on substance P and alpha-melanocyte-stimulating hormone breakdown in the rat brain.". J. Neurochem. 84 (5): 919–29. doi:10.1046/j.1471-4159.2003.01536.x. PMID 12603817.
External links
- MeSH prolyl+endopeptidase,+human
- Prolyl Endopeptidase entry at the National Center for Biotechnology Information
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