“Potato carboxypeptidase inhibitor”的意思、由来-开放百科全书

词条

Potato carboxypeptidase inhibitor

释义

Medicinal properties
References
Further reading
See also

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|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|2,3,4|a}}

Medicinal properties

Because of the structural similarities with EGF, PCI inhibits tumor cell growth.{{ref|5|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.{{ref|6|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).{{ref|7,8|a}}

References

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

Medicinal properties

References

Further reading

See also