title: Probing the CMP-Sialic Acid Donor Specificity of Two Human β-d-Galactoside Sialyltransferases (ST3Gal I and ST6Gal I) Selectively Acting on O- and N-Glycosylproteins.
abstract: Sialylation of glycoproteins and glycolipids is catalyzed by sialyltransferases in the Golgi of mammalian cells, whereby sialic acid residues are added at the nonreducing ends of oligosaccharides. Because sialylated glycans play critical roles in a number of human physio-pathological processes, the past two decades have witnessed the development of modified sialic acid derivatives for a better understanding of sialic acid biology and for the development of new therapeutic targets. However, nothing is known about how individual mammalian sialyltransferases tolerate and behave towards these unnatural CMP-sialic acid donors. In this study, we devised several approaches to investigate the donor specificity of the human β-d-galactoside sialyltransferases ST6Gal I and ST3Gal I by using two CMP-sialic acids: CMP-Neu5Ac, and CMP-Neu5N-(4pentynoyl)neuraminic acid (CMP-SiaNAl), an unnatural CMP-sialic acid donor with an extended and functionalized N-acyl moiety.
authors.affiliation: Université de Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000, Lille, France.
authors.forename: Maxence
authors.initials: M
authors.lastname: Noel
authors.affiliation: Université de Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000, Lille, France.
authors.forename: Pierre-André
authors.initials: PA
authors.lastname: Gilormini
authors.affiliation: Université de Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000, Lille, France.
authors.forename: Virginie
authors.identifier: 0000-0002-2572-4959
authors.initials: V
authors.lastname: Cogez
authors.affiliation: Université de Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000, Lille, France.
authors.forename: Nao
authors.initials: N
authors.lastname: Yamakawa
authors.affiliation: Université de Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000, Lille, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Vicogne
authors.affiliation: Université de Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000, Lille, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Lion
authors.affiliation: Université de Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000, Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Biot
authors.affiliation: Université de Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000, Lille, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Guérardel
authors.affiliation: Université de Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000, Lille, France.
authors.forename: Anne
authors.identifier: 0000-0002-1233-3799
authors.initials: A
authors.lastname: Harduin-Lepers
mesh_terms: D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D003001:Cloning, Molecular; D003568:Cytidine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression; D006017:Glycolipids / Q000737:chemistry / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D000216:N-Acylneuraminate Cytidylyltransferase / Q000235:genetics / Q000378:metabolism; D009345:Neisseria meningitidis / Q000737:chemistry / Q000201:enzymology; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism*; D012799:Sialyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D001426:Bacterial Proteins; D003568:Cytidine Monophosphate; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; D006017:Glycolipids; D006023:Glycoproteins; D000216:N-Acylneuraminate Cytidylyltransferase; D011134:Polysaccharides; D011994:Recombinant Proteins; D012794:Sialic Acids; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C561601:cytidine-5'-monophosphosialic acid; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
keywords: CMP-sialic acid; glycoengineering; selective exo enzymatic labeling; sialylation; sialyltransferases