5v6j | pdb_00005v6j

Glycan binding protein Y3 from mushroom Coprinus comatus possesses anti-leukemic activity

spinqualitylabelsall models 5v6j, resolution 1.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5v6j is a 4 chain structure with sequence from Coprinus comatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.18Å Ligands: NHE, PCA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G3BK00_COPCM Publication Abstract from PubMed Glycans possess significant chemical diversity; glycan binding proteins (GBPs) recognize specific glycans to translate their structures to functions in various physiological and pathological processes. Therefore, the discovery and characterization of novel GBPs and characterization of glycan-GBP interactions are significant to provide potential targets for therapeutic intervention of many diseases. Here, we report the biochemical, functional, and structural characterization of a 130-amino-acid protein, Y3, from the mushroom Coprinus comatus Biochemical studies of recombinant Y3 from a yeast expression system demonstrated the protein is a unique GBP. Additionally, we show that Y3 exhibits selective and potent cytotoxicity toward human T-cell leukemia Jurkat cells compared with a panel of cancer cell lines via inducing caspase-dependent apoptosis. Screening of a glycan array demonstrated GalNAcbeta1-4(Fucalpha1-3)GlcNAc (LDNF) as a specific Y3-binding ligand. To provide a structural basis for function, the crystal structure was solved to a resolution of 1.2 A, revealing a single-domain alphabetaalpha-sandwich motif. Two monomers were dimerized to form a large 10-stranded, antiparallel beta-sheet flanked by alpha-helices on each side, representing a unique oligomerization mode among GBPs. A large glycan binding pocket extends into the dimeric interface, and docking of LDNF identified key residues for glycan interactions. Disruption of residues predicted to be involved in LDNF/Y3 interactions resulted in the significant loss of binding to Jurkat T-cells and severely impaired their cytotoxicity. Collectively, these results demonstrate Y3 to be a GBP with selective cytotoxicity toward human T-cell leukemia cells and indicate its potential use in cancer diagnosis and treatment. Cytotoxic protein from the mushroom Coprinus comatus possesses a unique mode for glycan binding and specificity.,Zhang P, Li K, Yang G, Xia C, Polston JE, Li G, Li S, Lin Z, Yang LJ, Bruner SD, Ding Y Proc Natl Acad Sci U S A. 2017 Aug 22;114(34):8980-8985. doi:, 10.1073/pnas.1706894114. Epub 2017 Aug 7. PMID:28784797 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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