A proposed role for Leishmania major carboxypeptidase in peptide catabolism

• Published in: Biochemical and biophysical research communications Vol. 373; no. 1; pp. 25 - 29
• Main Authors: Isaza, Clara E., Zhong, Xuejun, Rosas, Lucia E., White, James D., Chen, Rita P.-Y., Liang, George F.-C., Chan, Sunney I., Satoskar, Abhay R., Chan, Michael K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2008
• Subjects: Amino Acid Sequence; Animals; Carboxypeptidases - chemistry; Carboxypeptidases - genetics; Carboxypeptidases - metabolism; Leishmania; Leishmania major; Leishmania major - genetics; Leishmania major - metabolism; M32 carboxypeptidase; Metalloprotease; Peptides - chemistry; Peptides - metabolism; Protozoan Proteins - chemistry; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Stage-specific expression; Substrate Specificity; Metalloprotease; Stage-specific expression; M32 carboxypeptidase; Leishmania
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.05.162

Leishmaniasis is a tropical disease caused by Leishmania, eukaryotic parasites transmitted to humans by sand flies. Towards the development of new chemotherapeutic targets for this disease, biochemical and in vivo expression studies were performed on one of two M32 carboxypeptidases present within the Leishmania major ( LmaCP1) genome. Enzymatic studies reveal that like previously studied M32 carboxypeptidases, LmaCP1 cleaves substrates with a variety of C-terminal amino acids—the primary exception being those having C-terminal acidic residues. Cleavage assays with a series of FRET-based peptides suggest that LmaCP1 exhibits a substrate length restriction, preferring peptides shorter than 9–12 amino acids. The in vivo expression of LmaCP1 was analyzed for each major stage of the L. major life cycle. These studies reveal that LmaCP1 expression occurs only in procyclic promastigotes—the stage of life where the organism resides in the abdominal midgut of the insect. The implications of these results are discussed.