4mps | pdb_00004mps
Crystal structure of rat Beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1), Northeast Structural Genomics Consortium Target RnR367A
Structural highlights
FunctionSIAT1_RAT Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates.[1] [2] [3] Publication Abstract from PubMedGlycan structures on glycoproteins and glycolipids play critical roles in biological recognition, targeting, and modulation of functions in animal systems. Many classes of glycan structures are capped with terminal sialic acid residues, which contribute to biological functions by either forming or masking glycan recognition sites on cell surface or secreted glycoconjugates. Sialylated glycans are synthesized in mammals by a single conserved family of sialyltransferases that have diverse linkage and acceptor specificities. We examined the enzymatic basis for glycan sialylation in animal systems by determining the crystal structure of rat ST6GAL1, an enzyme that creates terminal alpha2,6-sialic acid linkages on complex type N-glycans, at 2.4A resolution. Crystals were obtained from enzyme preparations generated in mammalian cells. The resulting structure revealed an overall protein fold broadly resembling the previously determined structure of pig ST3GAL1, including a CMP-sialic acid binding site assembled from conserved sialylmotif sequence elements. Significant differences in structure and disulfide bonding pattern were found outside the sialylmotif sequences, including differences in residues predicted to interact with the glycan acceptor. Computational substrate docking and molecular dynamics simulations were performed to predict and evaluate CMP-sialic acid donor and glycan acceptor interactions and the results were compared with kinetic analysis of active site mutants. Comparisons of the structure with pig ST3GAL1 and a bacterial sialyltransferase revealed a similar positioning of donor, acceptor, and catalytic residues that provide a common structural framework for catalysis by the mammalian and bacterial sialyltransferases. Enzymatic basis for N-glycan sialylation: structure of rat alpha2,6-sialyltransferase (ST6GAL1) reveals conserved and unique features for glycan sialylation.,Meng L, Forouhar F, Thieker D, Gao Z, Ramiah A, Moniz H, Xiang Y, Seetharaman J, Milaninia S, Su M, Bridger R, Veillon L, Azadi P, Kornhaber G, Wells L, Montelione GT, Woods RJ, Tong L, Moremen KW J Biol Chem. 2013 Oct 23. PMID:24155237[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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