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.[1]
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.[2,3,4]


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[edit] Medicinal properties

Because of the structural similarities with EGF, PCI inhibits tumor cell growth.[5] 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.[6]
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).[7,8]

[edit] References

  1.   Hass, J. M., and Ryan, C. A. (1981) Methods Enzymol. 80, 778-791.
  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
  3. a  The cystine-knot growth-factor superfamily. Sun, P. D. (1995) Annu. Rev. Biophys. Biomol. Struct. 24, 269-291. PMID 7663117
  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
  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 Free text
  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
  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
  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 Free text

[edit] Further reading

  • 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. Free text
  • Chang JY, Canals F, Schindler P, Querol E, Avilés FX (1994). "The disulfide folding pathway of potato carboxypeptidase inhibitor". J Biol Chem. 269 (35): 22087–94. PMID 3039909. 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

[edit] See also

Scaffold (disambiguation)
Protein kinase
Chemotherapy
Thrombolysis
Cancer research