5ajn

Crystal structure of the inactive form of GalNAc-T2 in complex with the glycopeptide MUC5AC-Cys13

spinqualitylabelsall models 5ajn, resolution 1.67Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ajn is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: A2G, EDO, SO4 Related: 5ajo, 5ajp Activity: Polypeptide N-acetylgalactosaminyltransferase, with EC number 2.4.1.41 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity and relies on a flexible linker located between the catalytic and the lectin domains. Our results also shed light on how GalNAc-Ts generate dense decoration of proteins with O-glycans. Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation.,Lira-Navarrete E, de Las Rivas M, Companon I, Pallares MC, Kong Y, Iglesias-Fernandez J, Bernardes GJ, Peregrina JM, Rovira C, Bernado P, Bruscolini P, Clausen H, Lostao A, Corzana F, Hurtado-Guerrero R Nat Commun. 2015 May 5;6:6937. doi: 10.1038/ncomms7937. PMID:25939779 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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