DS-epi1 and 2 share a common N-terminal epimerase domain (Fig. 2A) with 51% amino acid sequence identity between the two enzymes. The secondary and tertiary structures of this domain in the two enzymes are very similar. DS-epi1 has a C-terminal domain of unknown function and three-dimensional structure. There is a similarly positioned domain in DS-epi2 with unknown function and structure. These two domains in the two epimerases do not have significant homology. In addition, in DS-epi2, there is a C-terminal domain, which has 16% amino acid identity with chondroitin-O-sulfotransferase 1, recognized in the database as a CS/DS–O-sulfotransferase domain (Fig. 2A), suggesting that DS-epi2 is an enzyme with dual epimerase and O-sulfotransferase activity. Other enzymes for GAG biosynthesis have been shown to accommodate dual activities 17,18. The functional epimerase domain of the DS epimerases comprises two structural domains: one mainly composed of α-helices and one of β-sheets (Fig. 2B). These two domains of DS-epi1 were modelled on the crystal structure of heparinase II 19. At their boundary, they form a groove, where the substrate is positioned. Some amino acids that are
