The glucosinolate-myrosinase system. New insights into enzyme-substrate interactions by use of simplified inhibitors.
Myrosinase, a thioglucoside glucohydrolase, is the only enzyme able to hydrolyse glucosinolates, a unique family of molecules bearing an anomeric O-sulfated thiohydroximate function. Non-hydrolysable myrosinase inhibitors have been devised and studied for their biological interaction. Diverse modifications of the O-sulfate moiety did not result in a significant inhibitory effect, whereas replacing the D-glucopyrano residue by its carba-analogue allowed inhibition to take place. X-Ray experiments carried out after soaking allowed for the first time inclusion of a non-hydrolysable inhibitor inside the enzymatic pocket. Structural tuning of the aglycon part in its pocket is being used as a guide for the development of simplified and more potent inhibitors.
Bourderioux
Aurélie
A
Institut de Chimie Organique et Analytique (ICOA), UMR 6005, Université d'Orléans, BP 6759, F-45067, Orléans Cedex 2, France.
Lefoix
Myriam
M
Gueyrard
David
D
Tatibouét
Arnaud
A
Cottaz
Sylvain
S
Arzt
Steffi
S
Burmeister
Wim P
WP
Rollin
Patrick
P
D003461:Crystallography; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005961:Glucosinolates / Q000737:chemistry*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D005961:Glucosinolates; D006026:Glycoside Hydrolases; C022739:thioglucosidase