College of Chemistry, Berkeley

ChemiCAL Science and Engineering

MATCHMAKER Rapamycin brings together two binding proteins, FKBP and FRB, by binding to both. This, in turn, brings together Loc and Cat, two parts of sulfotransferase. Cat then catalyzes the addition of sulfates (stars) to carbohydrates (squiggles), which are exported to the cell surface. courtesy Bertozzi lab

Controlling sugar sulfation in the Bertozzi lab

from Chemical & Engineering News

Researchers have seized control of the machinery for carbohydrate sulfation, a common type of sugar modification. The new technique could facilitate studies of the effects of carbohydrate sulfation levels and modification sites on development, disease, and other processes.

Carbohydrates are often modified with sulfate groups in the Golgi apparatus, a process catalyzed by sulfotransferases, and are then routed to their final cellular destinations. Chemistry professor and Howard Hughes Medical Institute investigator Carolyn R. Bertozzi and coworkers at the University of California, Berkeley, have now devised a small-molecule approach for controlling sugar sulfation [Proc. Natl. Acad. Sci. USA, 101, 16715 (2004)].

They divide a sulfotransferase into two parts--one containing a localization domain (Loc) that directs the enzyme to the Golgi membrane, and one containing the enzyme's catalytic center (Cat). They then create genes for two conjugates: Loc-FKBP, combining Loc and FK-506 binding protein; and Cat- FRB, a combination of Cat and FKBP-rapamycin binding protein.

Cells lacking endogenous sulfotransferase activity are genetically modified to express the two conjugates. The small molecule rapamycin can bind FKBP and FRB, so when added to the cells it brings FKBP and FRB together. This also brings the Loc and Cat domains together, turning on Golgi-based sulfation. The sulfation level is tunable: The more rapamycin you add, the more sulfation you get. Bertozzi and coworkers are currently collaborating to extend the technique from cells to whole animals such as mice.

"This is an exciting technique that promises to reveal new insights about how cells control a chemical process essential to life," says carbohydrate specialist Pamela A. Marino at the National Institute of General Medical Sciences, which helped fund the work. "We can begin to see how it may lead to practical benefits for human health."

Related sites:

Carolyn Bertozzi website

Chemical & Engineering News

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