Document Detail


Carboxypeptidase O is a glycosylphosphatidylinositol-anchored intestinal peptidase with acidic amino acid specificity.
MedLine Citation:
PMID:  21921028     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The first metallocarboxypeptidase (CP) was identified in pancreatic extracts more than 80 years ago and named carboxypeptidase A (CPA; now known as CPA1). Since that time, seven additional mammalian members of the CPA subfamily have been described, all of which are initially produced as proenzymes, are activated by endoproteases, and remove either C-terminal hydrophobic or basic amino acids from peptides. Here we describe the enzymatic and structural properties of carboxypeptidase O (CPO), a previously uncharacterized and unique member of the CPA subfamily. Whereas all other members of the CPA subfamily contain an N-terminal prodomain necessary for folding, bioinformatics and expression of both human and zebrafish CPO orthologs revealed that CPO does not require a prodomain. CPO was purified by affinity chromatography, and the purified enzyme was able to cleave proteins and synthetic peptides with greatest activity toward acidic C-terminal amino acids unlike other CPA-like enzymes. CPO displayed a neutral pH optimum and was inhibited by common metallocarboxypeptidase inhibitors as well as citrate. CPO was modified by attachment of a glycosylphosphatidylinositol membrane anchor to the C terminus of the protein. Immunocytochemistry of Madin-Darby canine kidney cells stably expressing CPO showed localization to vesicular membranes in subconfluent cells and to the plasma membrane in differentiated cells. CPO is highly expressed in intestinal epithelial cells in both zebrafish and human. These results suggest that CPO cleaves acidic amino acids from dietary proteins and peptides, thus complementing the actions of well known digestive carboxypeptidases CPA and CPB.
Authors:
Peter J Lyons; Lloyd D Fricker
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-07     Completed Date:  2011-12-27     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  39023-32     Citation Subset:  IM    
Affiliation:
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carboxypeptidases / genetics,  metabolism*
Dietary Proteins / metabolism
Dogs
GPI-Linked Proteins / genetics,  metabolism*
Glycosylphosphatidylinositols*
Humans
Hydrogen-Ion Concentration
Intestines / enzymology*
Intracellular Membranes / enzymology*
Zebrafish / genetics,  metabolism*
Zebrafish Proteins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
DA-004494/DA/NIDA NIH HHS; EY-194332/EY/NEI NIH HHS; R01 DA004494/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Dietary Proteins; 0/GPI-Linked Proteins; 0/Glycosylphosphatidylinositols; 0/Zebrafish Proteins; EC 3.4.-/Carboxypeptidases
Comments/Corrections

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