1pzk

Cholera Toxin B-Pentamer Complexed With N-Acyl Phenyl Galactoside 9h

spinqualitylabelsall models 1pzk, resolution 1.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1pzk is a 5 chain structure with sequence from Vibrio cholerae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.35Å Ligands: J12 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q57193_VIBCL Publication Abstract from PubMed With the aim of developing high-affinity mono and multivalent antagonists of cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) we are using the galactose portion of the natural receptor ganglioside GM1 as an anchoring fragment in structure-based inhibitor design efforts. In order to establish a better structure-activity relationship for guiding these studies, we designed and prepared a small focused library of twenty 3,5-substituted phenylgalactosides based on two previous leads. The compounds were tested for their ability to block CTB(5) binding to immobilized ganglioside receptor and compared to the two previous leads. The crystal structures of the most promising compounds bound to either CTB(5) or LTB(5) were then determined in order to understand the basis for affinity differences. The most potent new compound yielded a six-fold improvement over our benchmark lead m-nitrophenyl-alpha-d-galactopyranoside (MNPG), and a two-fold improvement in IC(50) over a newer MNPG derivative. These results support the notion that the m-nitrophenyl moiety of MNPG and its derivatives is an important element to retain in future optimization efforts. Additionally, a consensus binding-pocket for the alkylmorpholine or piperazine moiety present in all of the designed antagonists was established as an important area of the GM1 binding site to target in future work. 3,5-Substituted phenyl galactosides as leads in designing effective cholera toxin antagonists; synthesis and crystallographic studies.,Mitchell DD, Pickens JC, Korotkov K, Fan E, Hol WG Bioorg Med Chem. 2004 Mar 1;12(5):907-20. PMID:14980603 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cholera toxin 3D structures User:David Solfiell/sandbox 1

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