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
- ^ 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.
- ^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.
- ^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.
- ^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.
- ^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.
- ^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.
- ^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.
- ^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