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Saturation transfer difference (STD) 1 H‐NMR experiments and in silico docking experiments to probe the binding of N ‐acetylneuraminic acid and derivatives to Vibrio cholerae sialidase
Author(s) -
Haselhorst Thomas,
Wilson Jennifer C.,
Thomson Robin J.,
McAtamney Sarah,
Menting John G.,
Coppel Ross L.,
von Itzstein Mark
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20143
Subject(s) - sialidase , chemistry , vibrio cholerae , docking (animal) , stereochemistry , active site , sialic acid , neuraminic acid , binding site , cholera toxin , anomer , enzyme , biochemistry , bacteria , neuraminidase , biology , microbiology and biotechnology , medicine , nursing , genetics
Saturation transfer difference (STD) 1 H 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.