| Abstract | Many hexose sugars in bacteria undergo a variety of modifications, including oxidation/reduction, amination and acetylation, as part of biosynthesis into their final biologically-active forms. Enzymes that catalyze these reactions normally utilize nucleotide-linked sugar substrates, utilizing the nucleotide as an 'ancient handle' to bind and orient the sugar within the enzymes' active site. We and others have focused efforts on elucidating structure-function relationships for a subset of such biosynthetic enzymes, those associated with the synthesis of trideoxy-diacetamidohexoses, and the nonulsonate sugars subsequently derived from them. With structural information combined with site-directed mutagenesis, enzymatic analysis and molecular modeling, these studies have been essential to understanding the chemistry of how these enzymes bind their substrates and effect catalysis. Enzymes having different folds, such as N-acetyltransferases, can utilize different scaffolds to attain the same 4-acetamido-sugar product. In the case of dehydratases/epimerases and aminotransferases, the enzymes have a conserved structure, but utilize subtle differences within their active site to confer substrate binding and the nature of the final product. These studies depict the structural relationships between these enzymes, while at the same time high-lighting important differences that are beginning to reveal their function at the molecular level. |
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