TY - JOUR
T1 - Regulating Cell Surface Glycosylation by Small Molecule Control of Enzyme Localization
AU - Kohler, Jennifer J.
AU - Bertozzi, Carolyn R.
N1 - Funding Information:
We are grateful to Fei Liu and David Austin for supplying the DNA encoding FKBP, to Steven Rosen for the DNA encoding FucT7, to Dr. Marilyn Farquhar for the polyclonal rabbit serum against mannosidase II, and to Christopher de Graffenried for expert assistance with microscopy. J.J.K. was supported by a postdoctoral fellowship from the American Cancer Society (PF TBE-101932). This work was supported by a grant from the National Institutes of Health (GM 59907).
PY - 2003/12
Y1 - 2003/12
N2 - Cell surface carbohydrates mediate interactions between the cell and its environment. Glycosyltransferases responsible for synthesis of cell surface oligosaccharides are therefore essential administrators of cellular communication. These enzymes often comprise large families. Redundacy of related family members and embryonic lethality both complicate genetic methods for deconvoluting functions of glycosyltransferases. We report a chemical method in which the activity of an individual glycosyltransferase is controlled by a small molecule. The approach exploits the requirement of Golgi localization, a common feature of glycosyltransferase superfamily members. In our approach, the glycosyltransferase is separated into two domains, one that determines localization and one responsible for catalysis. Control of enzyme activity is achieved using a small molecule to regulate association of the two domains. We used this method to regulate production of sialyl Lewis x by α1,3-fucosyltransferase VII in living cells.
AB - Cell surface carbohydrates mediate interactions between the cell and its environment. Glycosyltransferases responsible for synthesis of cell surface oligosaccharides are therefore essential administrators of cellular communication. These enzymes often comprise large families. Redundacy of related family members and embryonic lethality both complicate genetic methods for deconvoluting functions of glycosyltransferases. We report a chemical method in which the activity of an individual glycosyltransferase is controlled by a small molecule. The approach exploits the requirement of Golgi localization, a common feature of glycosyltransferase superfamily members. In our approach, the glycosyltransferase is separated into two domains, one that determines localization and one responsible for catalysis. Control of enzyme activity is achieved using a small molecule to regulate association of the two domains. We used this method to regulate production of sialyl Lewis x by α1,3-fucosyltransferase VII in living cells.
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U2 - 10.1016/j.chembiol.2003.11.018
DO - 10.1016/j.chembiol.2003.11.018
M3 - Article
C2 - 14700637
AN - SCOPUS:0346338103
SN - 1074-5521
VL - 10
SP - 1303
EP - 1311
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 12
ER -