6gxc | pdb_00006gxc

Bacterial oligosaccharyltransferase PglB in complex with an inhibitory peptide and a reactive lipid-linked oligosaccharide analog

spinqualitylabelsall models 6gxc, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6gxc is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FFK, MES, MN, NA, PEG NonStd Res: DAB, PPN Activity: Transferase, with EC number 2.4.99.19 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PGLB_CAMLR] Oligosaccharyltransferase that catalyzes the transfer of a preassembled heptasaccharide from a lipid donor to an asparagine residue in nascent polypeptide chains, affording a beta-linked glycan to the asparagine side chain of target proteins. Publication Abstract from PubMed Oligosaccharyltransferase (OST) is a key enzyme of the N-glycosylation pathway, where it catalyzes the transfer of a glycan from a lipid-linked oligosaccharide (LLO) to an acceptor asparagine within the conserved sequon N-X-T/S. A previous structure of a ternary complex of bacterial single subunit OST, PglB, bound to a non-hydrolyzable LLO analog and a wild type acceptor peptide showed how both substrates bind and how an external loop (EL5) of the enzyme provided specific substrate-binding contacts. However, there was a relatively large separation of the substrates at the active site. Here we present the X-ray structure of PglB bound to a reactive LLO analog and an inhibitory peptide, revealing previously unobserved interactions in the active site. We found that the atoms forming the N-glycosidic bond (C-1 of the GlcNAc moiety of LLO and the -NH2 group of the peptide) are closer than in the previous structure, suggesting that we have captured a conformation closer to the transition state of the reaction. We find that the distance between the divalent metal ion and the glycosidic oxygen of LLO is now 4 A, suggesting that the metal stabilizes the leaving group of the nucleophilic substitution reaction. Further, the carboxylate group of a conserved aspartate of PglB mediates an interaction network between the reducing-end sugar of the LLO, the asparagine side chain of the acceptor peptide, and a bound divalent metal ion. The interactions identified in this novel state are likely to be relevant in the catalytic mechanisms of all OSTs. Structure of bacterial oligosaccharyltransferase PglB bound to a reactive LLO and an inhibitory peptide.,Napiorkowska M, Boilevin J, Darbre T, Reymond JL, Locher KP Sci Rep. 2018 Nov 2;8(1):16297. doi: 10.1038/s41598-018-34534-0. PMID:30389987 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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