8v9q

Crystal structure of mGalNAc-T1 in complex with the mucin glycopeptide Muc5AC-13, Mn2+, and UDP.

spinqualitylabelsall models 8v9q, resolution 2.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8v9q is a 5 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.29Å Ligands: A2G, BMA, EDO, GOL, MAN, MN, NAG, SIN, UDP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GALT1_MOUSE 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 and Muc7. Publication Abstract from PubMed N-acetylgalactosaminyl-transferases (GalNAc-Ts) initiate mucin-type O-glycosylation, an abundant and complex posttranslational modification that regulates host-microbe interactions, tissue development, and metabolism. GalNAc-Ts contain a lectin domain consisting of three homologous repeats (alpha, beta, and gamma), where alpha and beta can potentially interact with O-GalNAc on substrates to enhance activity toward a nearby acceptor Thr/Ser. The ubiquitous isoenzyme GalNAc-T1 modulates heart development, immunity, and SARS-CoV-2 infectivity, but its substrates are largely unknown. Here, we show that both alpha and beta in GalNAc-T1 uniquely orchestrate the O-glycosylation of various glycopeptide substrates. The alpha repeat directs O-glycosylation to acceptor sites carboxyl-terminal to an existing GalNAc, while the beta repeat directs O-glycosylation to amino-terminal sites. In addition, GalNAc-T1 incorporates alpha and beta into various substrate binding modes to cooperatively increase the specificity toward an acceptor site located between two existing O-glycans. Our studies highlight a unique mechanism by which dual lectin repeats expand substrate specificity and provide crucial information for identifying the biological substrates of GalNAc-T1. An unusual dual sugar-binding lectin domain controls the substrate specificity of a mucin-type O-glycosyltransferase.,Collette AM, Hassan SA, Schmidt SI, Lara AJ, Yang W, Samara NL Sci Adv. 2024 Mar;10(9):eadj8829. doi: 10.1126/sciadv.adj8829. Epub 2024 Feb 28. PMID:38416819 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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