Saturation transfer difference (STD) 1H-NMR experiments and in silico docking experiments to probe the binding of N-acetylneuraminic acid and derivatives to Vibrio cholerae sialidase.

Autor: Haselhorst, Thomas, Wilson, Jennifer C., Thomson, Robin J., McAtamney, Sarah, Menting, John G., Coppel, Ross L., von Itzstein, Mark
Zdroj: Proteins; Aug2004, Vol. 56 Issue 2, p346-353, 8p
Abstrakt: Saturation transfer difference (STD) 1H NMR experiments were used to probe the epitope binding characteristics of the sialidase [EC 3.2.1.18] from the bacterium Vibrio cholerae, the causative agent of cholera. Binding preferences were investigated for N-acetylneuraminic acid (Neu5Ac, 1), the product of the sialidase catalytic reaction, for the known sialidase inhibitor 5-acetamido-2,6-anhydro-3,5-dideoxy- D- glycero- D- galacto-non-2-enoic acid (Neu5Ac2en, 2), and for the uronic acid-based Neu5Ac2en mimetic iso-propyl 2-acetamido-2,4-dideoxy-α- L- threo-hex-4-enopyranosiduronic acid ( 3), in which the native glycerol side-chain of Neu5Ac2en is replaced with an O-iso-propyl ether. The STD experiments provided evidence, supporting previous studies, that Neu5Ac ( 1) binds to the sialidase as the α-anomer. Docking experiments using DOCK (version 4.0.1) revealed further information regarding the binding characteristics of the enzyme active site in complex with Neu5Ac2en ( 2) and the Neu5Ac2en mimetic ( 3), indicating an expected dominant interaction of the acetamide moiety with the protein. Proteins 2004. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
Externí odkaz: