O-Sulfotransferase

In heparan sulfate biosynthesis, both N and O-sulfotransferases play pivotal roles. 2-O, 3-O and 6-O- Sulfotransferases catalyze the O-sulfation of heparan sulfate and their action results in the different O-sulfation patterns found. These patterns or motifs may play regulatory roles by interacting with different proteins, for example growth factors, in a specific way. If this is correct, strict regulation of the heparan sulfate biosynthesis would appear necessary.

How the biosynthetic machinery works is however poorly understood. Heterologously expressed O-sulfotransferases are now becoming available, and with them the possibility of studying their catalytic properties in detail. However, except for the enzymes, clearly defined substrates must be obtained. To probe the substrate preferences of the O-sulfotransferases, a panel of distinct oligosaccharides from the in vitro-generated heparan sulfate libraries was used.

Surprisingly, we found that the specificity of 6-O-sulfotransferase 3 towards substrates with distinct sulfation patterns was low: Jemth, P., Smeds, E., Do A. T., Hjertson, E., Kimata, E., Lindahl, U., and Kusche-Gullberg, M. (2003) Oligosaccharide library-based assessment of heparan sulfate 6-O-sulfotransferase substrate specificity. J. Biol. Chem. 278, 24371-24376 [abstract]