Sorting the diverse: The sequencebased classifications of carbohydrateactive enzymes

Carbohydrates offer a structural and chemical diversity unrivalled in Nature: two glucose residues can be joined together in 30 different ways, and, with six different sugars, the number of possible isomers exceeds 1012 [1]. This huge diversity is reflected in the diverse roles for carbohydrates in Nature. Mono, di, oligo and polysaccharides and glycoconjugates play myriad roles in biology, in addition to wellknown ones such as energy storage (starch, glycogen) and maintenance of structure (cellulose, chitin, alginate). The diversity of what is sometimes called the ‘glycome’ also provides for a subtle means of cellular communication in higher organisms: carbohydrates are the language of the cell. Sugarmediated interactions not only are important for the communication of healthy cells, but also play crucial roles in disease, viral invasion and bacterial attack and malignancy. Sharon [2] has termed the challenge of carbohydrates as “the last frontier of molecular and cell biology”. There is thus considerable interest in the enzymes whose job it is to modify and cleave carbohydrates [GHs (glycoside hydrolases) and lyases] and those involved in their biosynthesis, GTs (glycosyltransferases). Typically, these enzymes make up approx. 1–2% of the genome of any organism [3]. Thus, at the time of writing, there are around 70000 ORFs (open reading frames) known which potentially encode GHs or GTs. A major goal for the scientific community is to extract useful informa tion on the enzymes encoded by these ORFs from sequence alone. This is an enormous challenge, one complicated by the modular nature of the enzymes themselves [4].