Insights into the recognition of the human glycome by microbial carbohydrate-binding modules

Abstract

Mammalian glycans are often very complex and consequently both commensal bacteria and bacterial pathogens have developed specialized and often elaborate carbohydrate-active enzyme (CAZyme) systems to interact with these sugars. These enzymes are frequently multimodular, with modular functions most often conferring catalysis (glycoside hydrolase catalytic modules) or carbohydrate-binding (carbohydrate-binding modules or CBMs). Structure-function studies of five CBM families are revealing specificities for complex mammalian carbohydrates. Three of these CBM families (32, 47, and 51) show significant structural identity between their β-sandwich folds, suggesting a shared evolutionary precursor, but have divergent binding specificities. The family 40 and 41 CBMs recognize sialic acid and glycogen, respectively, through different modes of sugar binding, though they also adopt all β-structure folds. A structural view of new models generated for complete CAZymes suggests three distinct modes of CBM deployment: (i) formation of the catalytic site, (ii) coordinated catalysis and binding, and (iii) general substrate adherence.