請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/70378
標題: Kinetics and Protein-Inhibitor Docking Studies of Enantiomers of exo-2-Norbornyl-N-n-butylcarbamates as Pseudomonas Lipase Inhibitors to Probe the Enantioselectivity of the Enzyme
作者: Shen, Y.F.
Lin, G.
關鍵字: Lipase
Inhibitor
Carbamate
Enantioselectivity
cholesterol esterase
species lipase
automated docking
open
conformation
stereoselective inhibition
triacylglycerol lipase
lipolytic enzymes
crystal-structure
cepacia lipase
active-site
期刊/報告no:: Journal of the Chinese Chemical Society, Volume 59, Issue 1, Page(s) 60-65.
摘要: The Pseudomonas species lipase inhibition shows enantioselectivity for R-enantiomer over S-enantiomer of exo-2-norbornyl-N-n-butylcarbamates. R-, S-, and racemic-exo-2-norbornyl-N-n-butylcarbamates are all characterized as pseudo substrate inhibitors of the enzyme. Thus, the mechanism for Pseudomonas species lipase-catalyzed hydrolysis of the inhibitor is formation of the first enzyme-inhibitor Michaelis complex via nucleophilic attack of the active site serine to the inhibitor (K(i) step) then formation of the butylcarbamyl enzyme intermediate from this complex (k(2) step). Comparison of bimolecular rate constants (k(i) = k(2) / K(i)) of the inhibitors indicates that R-enantiomer is 1.8 times more potent than S-enantiomer. Thus, Pseudomonas species lipase shows enantioselectivity of 1.8 for R-exo-2-norbornyl-N-n-butylcarbamate over S-exo-2-norbornyl-N-n-butylcarbamate. Protein-ligand interaction studies on both enantiomers of exo-2-norbornyl-N-n-butylcarbamate as inhibitors of Pseudomonas species lipase using AutoDock suggest that R-enantiomer binds more tightly into the active site of the enzyme than S-enantiomer. The norbornyl ring of S-exo-2-norbornyl-N-n-butylcarbamate is repulsive to Ser 82 and His 251 of the catalytic triad as well as to Met 16 of the oxyanion hole. These repulsions may create few unfavorable interactions between S-exo-2-norbornyl-N-n-butylcarbamate and the enzyme and make this inhibitor a less potent one.
URI: http://hdl.handle.net/11455/70378
ISSN: 0009-4536
文章連結: http://dx.doi.org/10.1002/jccs.201100252
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