<p>O-Glycosyl hydrolases <db_xref db="EC" dbkey="3.2.1."/> are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [<cite idref="PUB00004870"/>, <cite idref="PUB00005266"/>]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site.</p><p>Glycosyl hydrolase family 27, family 31 and family 36 alpha-galactosidases form the glycosyl hydrolase clan GH-D (<db_xref db="CAZY" dbkey="acc_GH"/>), a superfamily of alpha-galactosidases, alpha-N-acetylgalactosaminidases, and isomaltodextranases which are likely to share a common catalytic mechanism and structural topology.</p><p>Alpha-galactosidase (<db_xref db="EC" dbkey="3.2.1.22"/>) (melibiase) [<cite idref="PUB00000002"/>] catalyzes the hydrolysis ofmelibiose into galactose and glucose. In man, the deficiency of this enzyme isthe cause of Fabry's disease (X-linked sphingolipidosis). Alpha-galactosidaseis present in a variety of organisms. There is a considerable degree ofsimilarity in the sequence of alpha-galactosidase from various eukaryoticspecies.<taxon tax_id="562">Escherichia coli</taxon> alpha-galactosidase (gene melA), which requires NAD andmagnesium as cofactors, is not structurally related to the eukaryotic enzymes;by contrast, an <taxon tax_id="562">Escherichia coli</taxon> plasmid encoded alpha-galactosidase (generafA <db_xref db="SWISSPROT" dbkey="P16551"/>) [<cite idref="PUB00002094"/>] contains a region of about 50 amino acids which is similar to adomain of the eukaryotic alpha-galactosidases.Alpha-N-acetylgalactosaminidase (<db_xref db="EC" dbkey="3.2.1.49"/>) [<cite idref="PUB00002595"/>] catalyzes the hydrolysis ofterminal non-reducing N-acetyl-D-galactosamine residues in N-acetyl-alpha-D-galactosaminides. In man, the deficiency of this enzyme is the cause ofSchindler and Kanzaki diseases. The sequence of this enzyme is highly relatedto that of the eukaryotic alpha-galactosidases.</p>