Inverting O-glycosidases

The reactions catalysed by these enzymes invariably involve a single chemical transition state, of the exploded nature described in Chapter 3, with varying mechanisms for activating nucleophile and leaving group, and varying degrees 

As might be expected from the fact that the extra methylene group in the glutamate side-chain makes the carboxylic acid group less acidic than that of aspartate, in only one family, where the stereochemistry is not experimentally determined (90), is there any suggestion of a system where glutamate is the base and aspartate is the acid. 

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Whether retaining or inverting, O-glycosidases have a number of common features ... 

Retaining and inverting O-glycosidases make use of a general acid/general base pair comprised of a carboxylic acid and carboxylate of aspartic acid or glutamic acid side chains (see also Eig. 21). These side chains have similar values in solution but the micro-environments of enzyme active sites allow each pK to be tuned so that each side chain is in the correct protonation state. This makes it possible for a carboxylate and a carboxylic acid to exist in the active site simultaneously. 

Glycosyl transferases and O-glycosidases modify glycoproteins and are important for polysaccharide catabolism. Inhibitors of these enzymes are potential drugs in the treatment of cancer, viral infection and diabetes. There are two mechanistic classes of glycosidases, retaining and inverting." ... 

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