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.ref_N|1|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.ref_N|2,3,4|a

Medicinal properties

Because of the structural similarities with EGF, PCI inhibits tumor cell growth.ref_N|5|a Mechanism of action is inhibition of receptor dimerization and receptor trans-autophosphorylation induced by epidermal growth factor (EGF) and by transforming growth factor alpha (TGF-alpha). Moreover, PCI blocks the formation and activation of ErbB1/ErbB-2 (EGFR and HER2) heterodimers that have a prominent role in carcinoma development.ref_N|6|a
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).ref_N|7,8|a

References

#note_N|1| "Hass, J. M., and Ryan, C. A. (1981) Methods Enzymol. 80, 778-791."
#note_N|2|a A structural superfamily of growth factors containing a cystine knot motif. "McDonald, N. Q., and Hendrickson, W. A. (1993) Cell 73, 421-424." PMID 8490958
#note_N|3|a The cystine-knot growth-factor superfamily. "Sun, P. D. (1995) Annu. Rev. Biophys. Biomol. Struct. 24, 269-291." PMID 7663117
#note_N|4|a A disulphide-reinforced structural scaffold shared by small proteins with diverse functions. "Ling, S. L., and Nussinov, R. (1995) Nat. Struct. Biol. 2, 835-837." PMID 7552703
#note_N|5|a Potato Carboxypeptidase Inhibitor, a T-knot Protein, Is an Epidermal Growth Factor Antagonist That Inhibits Tumor Cell Growth. "Blanco-Aparicio C, Molina MA, Fernández-Salas E, Frazier ML, Mas JM, Querol E, Avilés FX, de Llorens R. J Biol Chem, Vol. 273, Issue 20, 12370-12377, May 15, 1998." PMID 9575190 [http://www.jbc.org/cgi/content/full/273/20/12370 Free text]
#note_N|6|a Mechanism of action of potato carboxypeptidase inhibitor (PCI) as an EGF blocker. "Sitjà-Arnau M, Molina MA, Blanco-Aparicio C, Ferrer-Soler L, Lorenzo J, Avilés FX, Querol E, de Llorens R. Cancer Lett. 2005 Aug 26;226(2):169-84." PMID 16039955
#note_N|7|a An inhibitor of activated thrombin-activatable fibrinolysis inhibitor potentiates tissue-type plasminogen activator-induced thrombolysis in a rabbit jugular vein thrombolysis model. Nagashima M, Werner M, Wang M, Zhao L, Light DR, Pagila R, Morser J, Verhallen P. "Thromb Res. 2000 May 15;98(4):333-42." PMID 10822080
#note_N|8|a Plasma carboxypeptidases as regulators of the plasminogen system. Redlitz, A., Tan, A. K., Eaton, D. L., and Plow, E. F. "J Clin Invest. 1995 Nov;96(5):2534-8." PMID 7593646 [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=7593646 Free text]

Further reading

PBB_Further_reading
citations =
*Ryan, C. A., Hass, G. M., and Kuhn, R. W. (1974). "Purification and properties of a carboxypeptidase inhibitor from potatoes". "J. Biol. Chem. 249, 5495-5499." PMID 4415398. [http://www.jbc.org/cgi/reprint/249/17/5495 Free text]
*cite journal | author=Chang JY, Canals F, Schindler P, Querol E, Avilés FX |title=The disulfide folding pathway of potato carboxypeptidase inhibitor |journal=J Biol Chem. |volume=269 |issue=35 |pages= 22087–94 |year= 1994 |pmid= 3039909 |doi= |PMID 8071332 [http://www.jbc.org/cgi/content/abstract/269/35/22087 Free text]
*Smith JA, Francis SH, Corbin JD. "Autophosphorylation: a salient feature of protein kinases." "Mol Cell Biochem. 1993 Nov;127-128:51-70." PMID 7935362

ee also

Scaffold (disambiguation)

Protein kinase

Chemotherapy

Thrombolysis

Cancer research