Potato carboxypeptidase inhibitor

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Potato carboxypeptidase inhibitor (PCI) is a naturally occurring protease inhibitor peptide in potatoes that can form complexes with several metallo-carboxypeptidases, inhibiting them in a strong competitive way with a Ki in the nanomolar range.^a
PCI consists of 39 amino acids (MW 4295 Da) forming a 27-residue globular core stabilized by three disulfide bridges and a C-terminal tail with residues 35-39. PCI contains a small cysteine-rich module, called a T-knot scaffold, that is shared by several different protein families, including the EGF family.^a

Medicinal properties

Because of the structural similarities with EGF, PCI inhibits tumor cell growth.^a Mechanism of action is inhibition of receptor dimerization and receptor trans-autophosphorylation induced by epidermal growth factor (EGF). PCI blocks the formation and activation of ErbB1/ErbB-2 (EGFR and HER2) heterodimers that have a prominent role in carcinoma development.^a
PCI also inhibits transforming growth factor alpha (TGF-alpha). In addition for pancreatic enzymes carboxypeptidase A and B, PCI also inhibits carboxypeptidase R without affecting the activity of carboxypeptidase N in the circulation and have therefore use in thrombolytic therapy (blood clot lysis).^a

References

1. ^ Hass JM, Ryan CA (1981). "Carboxypeptidase inhibitor from potatoes". Methods Enzymol.. Methods in Enzymology 80 (Proteolytic Enzymes, Part C): 778–91. doi:10.1016/S0076-6879(81)80060-2. ISBN 978-0-12-181980-4. 
2. ^a McDonald NQ, Hendrickson WA (May 1993). "A structural superfamily of growth factors containing a cystine knot motif". Cell 73 (3): 421–4. doi:10.1016/0092-8674(93)90127-C. PMID 8490958. http://linkinghub.elsevier.com/retrieve/pii/0092-8674(93)90127-C. 
3. ^a Sun PD, Davies DR (1995). "The cystine-knot growth-factor superfamily". Annu Rev Biophys Biomol Struct 24: 269–91. doi:10.1146/annurev.bb.24.060195.001413. PMID 7663117. http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.bb.24.060195.001413?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov. 
4. ^a Lin SL, Nussinov R (October 1995). "A disulphide-reinforced structural scaffold shared by small proteins with diverse functions". Nat. Struct. Biol. 2 (10): 835–7. doi:10.1038/nsb1095-835. PMID 7552703. 
5. ^a Blanco-Aparicio C, Molina MA, Fernández-Salas E, et al. (May 1998). "Potato carboxypeptidase inhibitor, a T-knot protein, is an epidermal growth factor antagonist that inhibits tumor cell growth". J. Biol. Chem. 273 (20): 12370–7. doi:10.1074/jbc.273.20.12370. PMID 9575190. http://www.jbc.org/cgi/content/full/273/20/12370. 
6. ^a Sitjà-Arnau M, Molina MA, Blanco-Aparicio C, et al. (August 2005). "Mechanism of action of potato carboxypeptidase inhibitor (PCI) as an EGF blocker". Cancer Lett. 226 (2): 169–84. doi:10.1016/j.canlet.2005.01.025. PMID 16039955. http://linkinghub.elsevier.com/retrieve/pii/S0304-3835(05)00039-X. 
7. ^a Nagashima M, Werner M, Wang M, et al. (May 2000). "An inhibitor of activated thrombin-activatable fibrinolysis inhibitor potentiates tissue-type plasminogen activator-induced thrombolysis in a rabbit jugular vein thrombolysis model". Thromb. Res. 98 (4): 333–42. doi:10.1016/S0049-3848(00)00184-5. PMID 10822080. http://linkinghub.elsevier.com/retrieve/pii/S0049-3848(00)00184-5. 
8. ^a Redlitz A, Tan AK, Eaton DL, Plow EF (November 1995). "Plasma carboxypeptidases as regulators of the plasminogen system". J. Clin. Invest. 96 (5): 2534–8. doi:10.1172/JCI118315. PMC 185916. PMID 7593646. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=185916. 

Further reading

See also

Scaffold (disambiguation)
Protein kinase
Chemotherapy
Thrombolysis
Cancer research