4czs

Discovery of Glycomimetic Ligands via Genetically-encoded Library of Phage displaying Mannose-peptides

spinqualitylabelsall models 4czs, resolution 1.73Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4czs is a 8 chain structure with sequence from Canavalia cathartica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, MN NonStd Res: 8LR, XSN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CONA_CANCT] Glucose/D-mannose specific lectin. Publication Abstract from PubMed We describe an approach to accelerate the search for competitive inhibitors for carbohydrate-recognition domains (CRDs). Genetically encoded fragment-based discovery (GE-FBD) uses selection of phage-displayed glycopeptides to dock a glycan fragment at the CRD and guide selection of synergistic peptide motifs adjacent to the CRD. Starting from concanavalin A (ConA), a mannose (Man)-binding protein, as a bait, we narrowed a library of 108 glycopeptides to 86 leads that share a consensus motif, Man-WYD. Validation of synthetic leads yielded Man-WYDLF that exhibited 40-50-fold enhancement in affinity over methyl alpha-d-mannopyranoside (MeMan). Lectin array suggested specificity: Man-WYD derivative bound only to 3 out of 17 proteins-ConA, LcH, and PSA-that bind to Man. An X-ray structure of ConA:Man-WYD proved that the trimannoside core and Man-WYD exhibit identical CRD docking, but their extra-CRD binding modes are significantly different. Still, they have comparable affinity and selectivity for various Man-binding proteins. The intriguing observation provides new insight into functional mimicry of carbohydrates by peptide ligands. GE-FBD may provide an alternative to rapidly search for competitive inhibitors for lectins. Genetically Encoded Fragment-Based Discovery of Glycopeptide Ligands for Carbohydrate-Binding Proteins.,Ng S, Lin E, Kitov PI, Tjhung KF, Gerlits OO, Deng L, Kasper B, Sood A, Paschal BM, Zhang P, Ling CC, Klassen JS, Noren CJ, Mahal LK, Woods RJ, Coates L, Derda R J Am Chem Soc. 2015 Apr 16. PMID:25860443 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Concanavalin A

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