Biosynthesis of L-selectin ligands: sulfation of sialyl Lewis x-related oligosaccharides by a family of GlcNAc-6-sulfotransferases

Biochemistry
K G BowmanC R Bertozzi

Abstract

The leukocyte adhesion molecule L-selectin mediates lymphocyte homing to secondary lymphoid organs and to certain sites of inflammation. The cognate ligands for L-selectin possess the unusual sulfated tetrasaccharide epitope 6-sulfo sialyl Lewis x (Siaalpha2-->3Galbeta1-->4[Fucalpha1-->3][SO(3)-->6]GlcNAc). Sulfation of GlcNAc within sialyl Lewis x is a crucial modification for L-selectin binding, and thus, the underlying sulfotransferase may be a key modulator of lymphocyte trafficking. Four recently discovered GlcNAc-6-sulfotransferases are the first candidate contributors to the biosynthesis of 6-sulfo sLex in the context of L-selectin ligands. Here we report the in vitro activity of the four GlcNAc-6-sulfotransferases on a panel of synthetic oligosaccharide substrates that comprise structural motifs derived from sialyl Lewis x. Each enzyme preferred a terminal GlcNAc residue, and was impeded by the addition of a beta1,4-linked Gal residue (i.e., terminal LacNAc). Surprisingly, for three of the enzymes, significant activity was observed with sialylated LacNAc, and two of the enzymes were capable of detectable sulfation of GlcNAc in the context of sialyl Lewis x. On the basis of these results, we propose possible pathways for...Continue Reading

References

Dec 5, 1988·FEBS Letters·J P KamerlingJ F Vliegenthart
May 12, 1995·The Journal of Biological Chemistry·R P McEverR D Cummings
May 19, 1995·The Journal of Biological Chemistry·S HemmerichS D Rosen
Sep 22, 1995·The Journal of Biological Chemistry·D Crommie, S D Rosen
Apr 1, 1994·European Journal of Biochemistry·C H HokkeJ F Vliegenthart
Aug 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·L V HooperJ U Baenziger
Jan 1, 1995·Current Opinion in Hematology·I Stamenkovic
Aug 26, 1998·The Journal of Biological Chemistry·K UchimuraT Muramatsu
Jan 16, 1999·Chemistry & Biology·K G Bowman, C R Bertozzi
Apr 27, 2000·The Journal of Biological Chemistry·H KitagawaK Sugahara

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Citations

Mar 1, 2005·Journal of the American Society for Mass Spectrometry·Hui JiangHeather Desaire
Sep 28, 2005·Journal of the American Society for Mass Spectrometry·Ying ZhangHeather Desaire
Jun 24, 2009·Journal of the American Society for Mass Spectrometry·Ming LeiMilos V Novotny
Dec 22, 2009·Journal of the American Society for Mass Spectrometry·Ming LeiYehia Mechref
Oct 7, 2004·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Linda C Giudice
Mar 17, 2004·Bioorganic & Medicinal Chemistry·Kenji SasakiKazukiyo Kobayashi
Nov 13, 2003·Bioorganic & Medicinal Chemistry Letters·Kenji SasakiKazukiyo Kobayashi
Mar 4, 2003·Chemical Communications : Chem Comm·Hirotaka UzawaNorihiko Minoura
Oct 20, 2004·Angewandte Chemie·Sarah R HansonChi-Huey Wong
Jul 10, 2003·Chembiochem : a European Journal of Chemical Biology·Hirotaka UzawaKazukiyo Kobayashi
Sep 30, 2011·Rapid Communications in Mass Spectrometry : RCM·Diarmuid T KennyNiclas G Karlsson
Jul 2, 2004·Organic Letters·Matthew R Pratt, Carolyn R Bertozzi
Feb 14, 2002·Chemical Reviews·Milton J Kiefel, Mark von Itzstein
Dec 3, 2004·Drug Discovery Today·Virginia L RathStefan Hemmerich
Jul 12, 2003·The Journal of Biological Chemistry·Christopher L de Graffenried, Carolyn R Bertozzi
Sep 10, 2002·The Journal of Biological Chemistry·Tomoya O AkamaMichiko N Fukuda
Dec 27, 2002·The Journal of Biological Chemistry·Xianlin HanDavid M Holtzman
Jun 29, 2004·The Journal of Biological Chemistry·Christopher L de Graffenried, Carolyn R Bertozzi
Jun 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Igor TvaroškaJaroslav Koča
Jul 4, 2009·Analytical Chemistry·Masaaki ToyodaAkihiko Kameyama
Jun 6, 2003·Journal of the American Chemical Society·Matthew R Pratt, Carolyn R Bertozzi

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