The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Microbial Serine Carboxypeptidase Inhibitors
Comparative Analysis of Actions on Homologous Enzymes Derived from Man, Yeast and Wheat
YURIE SATOHYOSHITO KADOTAYUKAKO OHEDAJUN KUWAHARASEIICHI AIKAWAFUMIKO MATSUZAWAHIROFUMI DOITAKAAKI AOYAGIHITOSHI SAKURABAKOHJI ITOH
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2004 Volume 57 Issue 5 Pages 316-325

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Abstract

The actions of peptidase inhibitors derived from Streptomycete on human cathepsin A (hCath A), yeast carboxypeptidase Y (CPY), and wheat carboxypeptidase II (CPW) were analyzed comparatively. Lactacystin and omuralide (clasto-lactacystin β-lactone), well-known cytoplasmic proteasome inhibitors, both had a potent and non-competitive inhibitory effect on these homologous serine carboxypeptidases, although they inhibited CPW and hCath A more effectively than CPY in vitro. Ebelactone B exhibited a mixed non-competitive inhibitory effect and selectivity for CPY. Piperastatin A showed competitive inhibition of CPY and hCath A but had little effect on CPW. In contrast, chymostatin inhibited CPW efficiently, while it had less effect on hCath A and CPY. In cell culture system, lactacystin was the most potent as to inactivation of the intralysosomal recombinant hCath A activity expressed in a genetically engineered fibroblastic cell line with galactosialidosis (hCath A deficiency). These results suggest that the specific inhibitory effects of lactacystin and its derivatives on hCath A might be applicable to elucidate the pathophysiological roles in the human deficieecy.

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