| Structural highlights
Function
[GALT2_HUMAN] Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region.[1] [2]
Publication Abstract from PubMed
Studying posttranslational modifications classically relies on experimental strategies that oversimplify the complex biosynthetic machineries of living cells. Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein, and disease-relevant biosynthetic regulation is currently elusive. Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure. We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell. We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases. This approach bestows a gain-of-chemical-functionality modification on cells, where the products of individual glycosyltransferases can be selectively characterized or manipulated to understand glycan contribution to major physiological processes.
Bump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells.,Schumann B, Malaker SA, Wisnovsky SP, Debets MF, Agbay AJ, Fernandez D, Wagner LJS, Lin L, Li Z, Choi J, Fox DM, Peh J, Gray MA, Pedram K, Kohler JJ, Mrksich M, Bertozzi CR Mol Cell. 2020 Jun 4;78(5):824-834.e15. doi: 10.1016/j.molcel.2020.03.030. Epub, 2020 Apr 22. PMID:32325029[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wandall HH, Hassan H, Mirgorodskaya E, Kristensen AK, Roepstorff P, Bennett EP, Nielsen PA, Hollingsworth MA, Burchell J, Taylor-Papadimitriou J, Clausen H. Substrate specificities of three members of the human UDP-N-acetyl-alpha-D-galactosamine:Polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2, and -T3. J Biol Chem. 1997 Sep 19;272(38):23503-14. PMID:9295285
- ↑ Iwasaki H, Zhang Y, Tachibana K, Gotoh M, Kikuchi N, Kwon YD, Togayachi A, Kudo T, Kubota T, Narimatsu H. Initiation of O-glycan synthesis in IgA1 hinge region is determined by a single enzyme, UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2. J Biol Chem. 2003 Feb 21;278(8):5613-21. Epub 2002 Nov 15. PMID:12438318 doi:http://dx.doi.org/10.1074/jbc.M211097200
- ↑ Schumann B, Malaker SA, Wisnovsky SP, Debets MF, Agbay AJ, Fernandez D, Wagner LJS, Lin L, Li Z, Choi J, Fox DM, Peh J, Gray MA, Pedram K, Kohler JJ, Mrksich M, Bertozzi CR. Bump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells. Mol Cell. 2020 Jun 4;78(5):824-834.e15. doi: 10.1016/j.molcel.2020.03.030. Epub, 2020 Apr 22. PMID:32325029 doi:http://dx.doi.org/10.1016/j.molcel.2020.03.030
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