Lysosomal carboxypeptidase

SC 6 Families of endopeptidases (oligopeptidases) and exopeptidases (including lysosomal carboxypeptidase A in family S10) Ser, Asp, His a,/3-Hydrolase... 

As expected for a lysosomal carboxypeptidase, the pH optimum for the proteolytic activity of CatA is found in the acidic range at pH 5.5 [7]. In a neutral pH environment, CatA is able to function as a deamidase converting amide-blocked peptides into the acidic form [15]. Because amidation at the C-terminus is required for the activity of many small signaling peptides [16], this observation... 

Hinek, A. et al (2008) Enzymatic activity of lysosomal carboxypeptidase (cathepsin) A is required for proper elastic fiber formation and inactivation of endothelin-1 Circulation, 117, 1973-1981. 

Pshezhetsky, A.V. (1998) Lysosomal carboxypeptidase A, in Handbook of Proteolytic Enzymes (ed. A.J. Barett), Academic Press, London, pp. 393-398. 

Cysteine carboxypeptidases Cleave amino acids from C-terminal, cysteine in the active site Lysosomal carboxypeptidase B... 

A number of laboratories have reported the inactivation of liver aldolase by lysosomal proteinases, including not only cathepsins B and Bi (5-8), but also cathepsin L (9) and a lysosomal carboxypeptidase (8). However, the role of these lysosomal proteinases in the turnover or regulation of activity of these enzymes has remained unclear. 

Tranchemontagne, J., Michaud, L., and Potier, M., 1990, Deficient lysosomal carboxypeptidase activity in galactosialidosis, Biochem. Biophys. Res. Commun. 168 22-29. 

Drugs that have primary amino groups available for conjugation, for instance dopamine and doxorubicin, can in principle be coupled to LMWPs via oligopeptides. In contrast to the carboxypeptidases, the aminopeptidases appear to possess a broader specificity. To allow the release of terminal amino group-containing drugs in the acid environment of the lysosomes without the requirement of enzymes, an acid-sensitive spacer can be used. 

This enzyme [EC 3.4.16.5] (also known as serine-type carboxypeptidase I, cathepsin A, carboxypeptidase Y, and lysosomal protective protein) is a member of the peptidase family SIO and catalyzes the hydrolysis of the peptide bond, with broad specificity, located at the C-terminus of a polypeptide. The pH optimum ranges from 4.5 to 6.0. The enzyme is irreversibly inhibited by diisopropyl fluorophosphate and is sensitive to thiolblocking reagents. 

Cysteine proteases are so called because of a critical cysteine involved (together with an adjacent histidine) in the catalytic mechanism. Cysteine proteases include papain-related proteases, calpain-related proteases and the caspases. Papain-like cysteine proteases include the plant enzymes actinidin, aleurain, bromelain, caricain, chymopapain, ficin and papain and the lysosomal cathepsins B, C, H, K, L and S. Cathepsin C is multimeric (MW -200,000), but the other papain-related proteases are monomeric with MWs of about 20,000-35,000. While cathepsin C is a dipeptidyl aminopeptidase, the other enzymes are endopeptidases. Cathepsin B is an endopeptidase and a dipeptidyl carboxypeptidase. Cathepsin H is an endopeptidase and an aminopeptidase. In higher animals, cathepsin B generates peptides from antigens for presentation to T cells by the major histocompatibility... 

Clan SC contains peptidases with the a/P hydrolase fold bearing the catalytic triad in the order Ser, Asp, His. This clan includes the families (characteristic member in parentheses) S9 (prolyl oligopeptidase), S10 (carboxypeptidase C), S15 (Xaa-Pro dipeptidyl -peptidase), S28 (lysosomal Pro-Xaa carboxypeptidase), S33 (prolyl amino-peptidase), and S37 (Streptomyces PS-10 peptidase). The characteristic catalytic dyad Ser, Lys of dan SE is represented by the motif Ser-Xaa-Xbb-Lys, and the fold consists of helices and an a + P sandwich. The families of this clan Sll (penicillin-binding protein 5), S12 (Streptomyces R61 D-Ala-D-Ala carboxypeptidase), S13 (penicillinbinding protein 4) are involved in the biosynthesis, turnover and lysis of bacterial cell walls. 

When we incubate human bradykininogen (a partially pw-.ified preparation that our laboratory has prepared (6) with the lysosomal fraction or the extra-lysosomal fraction we can obtain kinin activity as demonstrated by the contractions of the guinea pig ileum or rat uterus. The kinin-forming activity is thus present apparently throughout the cell and we have recently discovered (7) that it is present in the nuclei. The kinin produced is completely destroyed by carboxypeptidase B. 

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