Inhibition of yeast lipase (CRL1) and cholesterol esterase (CRL3) by 6-chloro-2-pyrones: comparison with porcine cholesterol esterase.
作者： Mary Stoddard Hatch , William M Brown , Jason A Deck , Lucy A Hunsaker , Lorraine M Deck
DOI: 10.1016/S0167-4838(01)00304-1
关键词:
摘要: Previously, it was demonstrated that pancreatic cholesterol esterase is selectively inhibited by 6-chloro-2-pyrones with cyclic aliphatic substituents in the 3-position. Inhibition reversible and competitive substrate. Pancreatic a potential target for treatment of hypercholesterolemia. In present study, yeast from Candida cylindracea (also called C. rugosa CRL3) compared to porcine inhibition series 3-alkyl- or 5-alkyl-6-chloro-2-pyrones. addition, CRL3 related lipase CRL1. substituted binding substrate p-nitrophenyl butyrate. constants ranged 0.2 microM >90 microM. Small changes alkyl group had profound effects on binding. The pattern quite distinct observed esterase. Molecular modeling studies suggest orientation these inhibitors at active site can vary but pyrone ring consistently occupies position close serine. CRL1 highly homologous CRL3. Nevertheless, patterns differ markedly are slowly hydrolyzed presence pseudosubstrates CRL3, simple
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