4aml

CRYSTAL STRUCTURE OF WHEAT GERM AGGLUTININ ISOLECTIN 1 IN COMPLEX WITH GLYCOSYLURETHAN

spinqualitylabelsall models 4aml, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4aml is a 2 chain structure with sequence from Triticum aestivum. This structure supersedes the now removed PDB entry 2uwg. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: GOL, GYU, PCA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AGI1_WHEAT N-acetyl-D-glucosamine / N-acetyl-D-neuraminic acid binding lectin. Publication Abstract from PubMed The inhibition of carbohydrate-protein interactions by tailored multivalent ligands is a powerful strategy for the treatment of many human diseases. Crucial for the success of this approach is an understanding of the molecular mechanisms as to how a binding enhancement of a multivalent ligand is achieved. We have synthesized a series of multivalent N-acetylglucosamine (GlcNAc) derivatives and studied their interaction with the plant lectin wheat germ agglutinin (WGA) by an enzyme-linked lectin assay (ELLA) and X-ray crystallography. The solution conformation of one ligand was determined by NMR spectroscopy. Employing a GlcNAc carbamate motif with alpha-configuration and by systematic variation of the spacer length, we were able to identify divalent ligands with unprecedented high WGA binding potency. The best divalent ligand has an IC(50) value of 9.8 muM (ELLA) corresponding to a relative potency of 2350 (1170 on a valency-corrected basis, i.e., per mol sugar contained) compared to free GlcNAc. X-ray crystallography of the complex of WGA and the second best, closely related divalent ligand explains this activity. Four divalent molecules simultaneously bind to WGA with each ligand bridging adjacent binding sites. This shows for the first time that all eight sugar binding sites of the WGA dimer are simultaneously functional. We also report a tetravalent neoglycopeptide with an IC(50) value of 0.9 muM being 25 500 times higher than that of GlcNAc (6400 times per contained sugar) and the X-ray structure analysis of its complex with glutaraldehyde-cross-linked WGA. Comparison of the crystal structure and the solution NMR structure of the neoglycopeptide as well as results from the ELLA suggest that the conformation of the glycopeptide in solution is already preorganized in a way supporting multivalent binding to the protein. Our findings show that bridging adjacent protein binding sites by multivalent ligands is a valid strategy to find high-affinity protein ligands and that even subtle changes of the linker structure can have a significant impact on the binding affinity. Structural Basis of Multivalent Binding to Wheat Germ Agglutinin.,Schwefel D, Maierhofer C, Beck JG, Seeberger S, Diederichs K, Moller HM, Welte W, Wittmann V J Am Chem Soc. 2010 Jun 7. PMID:20527753 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Agglutinin 3D structures

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