An elaboration on the syn-anti proton donor concept of glycoside hydrolases:: electrostatic stabilisation of the transition state as a general strategy

An in silico survey of all known 3D-structures of glycoside hydrolases that contain a ligand in the -1 subsite is presented. A recurrent crucial positioning of active site residues indicates a common general strategy for electrostatic stabilisation directed to the carbohydrate's ring-oxygen at the transition state. This is substantially different depending on whether the enzyme's proton donor is syn or anti positioned versus the substrate. A comprehensive list of enzymes belonging to 42 different families is given and selected examples are described. An implication for an early evolution scenario of glycoside hydrolases is discussed. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.