Carboxypeptidase A: Difference between revisions
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== Other Ligands == | == Other Ligands == | ||
In addition to the inhibitory Zn<sup>2+</sup> ion, CPA can be inhibited by other ions and molecules. Some of these inhibitors include, but are not limited to, other metal ions and anions,<ref name=“Geoghegan 1983”>Geoghegan, KF, Galdes, A, Martinelli, RA, Holmquist, B, Auld, DS, Vallee, BL. 1983. Cryospectroscopy of intermediates in the mechanism of carboxypeptidase A. ''Biochem.'' 22(9):2255-2262. [http://pubs.acs.org/doi/abs/10.1021/bi00278a031 DOI: 10.1021/bi00278a031]</ref> phosphonates,<ref name=“Kaplan 1991”>Kaplan, AP, Bartlett, PA. 1991. Synthesis and evaluation of an inhibitor of carboxypeptidase A with a Ki value in the femtomolar range. ''Biochem.'' 30(33):8165-8170. [https://www.ncbi.nlm.nih.gov/pubmed/1868091 PMID: 1868091]</ref> cysteine, sulfides, and cyanide, the chelating agent 1,10-pentathroline,<ref name=“Manual”> Worthington, K., Worthington, V. 1993. Worthington Enzyme Manual: Enzymes and Related Biochemicals. Freehold (NJ): Worthington Biochemical Corporation; [2011; accessed March 28, 2017]. Carboxypeptidase A. http://www.worthington-biochem.com/COA/</ref> Ochratoxin A,<ref name=“Pitout 1969”>Pitout, MJ, Nel, W. 1969. The inhibitory effect of ochratoxin a on bovine carboxypeptidase a in vitro. ''Biochem. Pharma.'' 18(8):1837-1843. [https://doi.org/10.1016/0006-2952(69)90279-2 DOI: 0.1016/0006-2952(69)90279-2]</ref> and Latexin.<ref name=“Normant 1995”>Normant, E, Martres, MP, Schwartz, JC, Gros, C. 1995. Purification, cDNA cloning, functional expression, and characterization of a 26-kDa endogenous mammalian carboxypeptidase inhibitor. ''Proc. Natl. Acad. Sci.'' 92(26):12225-12229. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40329/ PMCID: PMC40329]</ref> | In addition to the inhibitory Zn<sup>2+</sup> ion, CPA can be inhibited by other ions and molecules. Some of these inhibitors include, but are not limited to, other metal ions and anions,<ref name=“Geoghegan 1983”>Geoghegan, KF, Galdes, A, Martinelli, RA, Holmquist, B, Auld, DS, Vallee, BL. 1983. Cryospectroscopy of intermediates in the mechanism of carboxypeptidase A. ''Biochem.'' 22(9):2255-2262. [http://pubs.acs.org/doi/abs/10.1021/bi00278a031 DOI: 10.1021/bi00278a031]</ref> phosphonates,<ref name=“Kaplan 1991”>Kaplan, AP, Bartlett, PA. 1991. Synthesis and evaluation of an inhibitor of carboxypeptidase A with a Ki value in the femtomolar range. ''Biochem.'' 30(33):8165-8170. [https://www.ncbi.nlm.nih.gov/pubmed/1868091 PMID: 1868091]</ref> [http://en.wikipedia.org/wiki/Cysteine cysteine], [http://en.wikipedia.org/wiki/Sulfide sulfides], and [http://en.wikipedia.org/wiki/Cyanide cyanide], the [http://scifun.chem.wisc.edu/CHEMWEEK/Chelates/Chelates.html chelating agent] [http://en.wikipedia.org/wiki/Phenanthroline 1,10-pentathroline],<ref name=“Manual”> Worthington, K., Worthington, V. 1993. Worthington Enzyme Manual: Enzymes and Related Biochemicals. Freehold (NJ): Worthington Biochemical Corporation; [2011; accessed March 28, 2017]. Carboxypeptidase A. http://www.worthington-biochem.com/COA/</ref> Ochratoxin A,<ref name=“Pitout 1969”>Pitout, MJ, Nel, W. 1969. The inhibitory effect of ochratoxin a on bovine carboxypeptidase a in vitro. ''Biochem. Pharma.'' 18(8):1837-1843. [https://doi.org/10.1016/0006-2952(69)90279-2 DOI: 0.1016/0006-2952(69)90279-2]</ref> and [http://en.wikipedia.org/wiki/Latexin_family Latexin].<ref name=“Normant 1995”>Normant, E, Martres, MP, Schwartz, JC, Gros, C. 1995. Purification, cDNA cloning, functional expression, and characterization of a 26-kDa endogenous mammalian carboxypeptidase inhibitor. ''Proc. Natl. Acad. Sci.'' 92(26):12225-12229. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40329/ PMCID: PMC40329]</ref> | ||
Detailed studies of anion inhibition have indicated that the nature of anion inhibition is partly competitive at the same binding site.<ref name="CPA1" /> In particular, the sulfate anion (SO<sub>4</sub><sup>2-</sup>) has been of interest to researchers. In a crystallized structure of carboxypeptidase T (PDB code: [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ord 1ORD]), a SO<sub>4</sub><sup>2-</sup> anion is found occupying a portion of a region that corresponds to the Arg127, Asn144, Arg145, and Tyr248 residues in the S1 subsite of CPA.<ref name="CPA1" /> In this case, it is understood that the SO<sub>4</sub><sup>2-</sup> anion prevents the recognition of the carboxylate group at the C-terminus of the polypeptide substrate. | Detailed studies of anion inhibition have indicated that the nature of anion inhibition is partly competitive at the same binding site.<ref name="CPA1" /> In particular, the sulfate anion (SO<sub>4</sub><sup>2-</sup>) has been of interest to researchers. In a crystallized structure of carboxypeptidase T (PDB code: [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ord 1ORD]), a SO<sub>4</sub><sup>2-</sup> anion is found occupying a portion of a region that corresponds to the Arg127, Asn144, Arg145, and Tyr248 residues in the S1 subsite of CPA.<ref name="CPA1" /> In this case, it is understood that the SO<sub>4</sub><sup>2-</sup> anion prevents the recognition of the carboxylate group at the C-terminus of the polypeptide substrate. | ||