Abstract
Sialyltransferases of the mammalian ST8Sia family catalyze oligo- and polysialylation of surface-localized glycoproteins and glycolipids through transfer of sialic acids from CMP-sialic acid to the nonreducing ends of sialic acid acceptors. The crystal structure of human ST8SiaIII at 1.85-Å resolution presented here is, to our knowledge, the first solved structure of a polysialyltransferase from any species, and it reveals a cluster of polysialyltransferase-specific structural motifs that collectively provide an extended electropositive surface groove for binding of oligo-polysialic acid chain products. The ternary complex of ST8SiaIII with a donor sugar analog and a sulfated glycan acceptor identified with a sialyltransferase glycan array provides insight into the residues involved in substrate binding, specificity and sialyl transfer.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites / genetics
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Cells, Cultured
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Chromatography, Thin Layer
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Crystallography, X-Ray
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Electrophoresis, Polyacrylamide Gel
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Glycosylation
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Humans
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Kinetics
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Mass Spectrometry / methods
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Neural Cell Adhesion Molecules / chemistry
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Neural Cell Adhesion Molecules / genetics
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Neural Cell Adhesion Molecules / metabolism
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Polysaccharides / chemistry
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Polysaccharides / metabolism
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Protein Binding
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Protein Structure, Tertiary*
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Sialic Acids / chemistry
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Sialic Acids / metabolism*
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Sialyltransferases / chemistry*
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Sialyltransferases / genetics
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Sialyltransferases / metabolism*
Substances
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Neural Cell Adhesion Molecules
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Polysaccharides
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Recombinant Proteins
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Sialic Acids
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polysialic acid
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Sia(alpha2,3)Gal(beta1,4)GlcNAc alpha-2,8-sialyltransferase
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Sialyltransferases