Potato carboxypeptidase inhibitor

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.
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.
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.
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.
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.
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.

Further reading

• Ryan CA, Hass GM, Kuhn RW (10 September 1974). "Purification and properties of a carboxypeptidase inhibitor from potatoes". J. Biol. Chem. 249 (17): 5495–9. PMID 4415398.
• Chang JY, Canals F, Schindler P, Querol E, Avilés FX (2 September 1994). "The disulfide folding pathway of potato carboxypeptidase inhibitor". J. Biol. Chem. 269 (35): 22087–94. PMID 8071332.
• Smith JA, Francis SH, Corbin JD (November 1993). "Autophosphorylation: a salient feature of protein kinases". Mol. Cell. Biochem. 127–128: 51–70. doi:10.1007/BF01076757. PMID 7935362.

See also

Scaffold (disambiguation)
Protein kinase
Chemotherapy
Thrombolysis
Cancer research