title: Protein Camouflage: Supramolecular Anion Recognition by Ubiquitin.
abstract: Progress in the field of bio-supramolecular chemistry, the bottom-up assembly of protein-ligand systems, relies on a detailed knowledge of molecular recognition. To address this issue, we have characterised complex formation between human ubiquitin (HUb) and four supramolecular anions. The ligands were: pyrenetetrasulfonic acid (4PSA), p-sulfonato-calix[4]arene (SCLX4), bisphosphate tweezers (CLR01) and meso-tetrakis (4-sulfonatophenyl)porphyrin (TPPS), which vary in net charge, size, shape and hydrophobicity. All four ligands induced significant changes in the HSQC spectrum of HUb. Chemical shift perturbations and line-broadening effects were used to identify binding sites and to quantify affinities. Supporting data were obtained from docking simulations. It was found that these weakly interacting ligands bind to extensive surface patches on HUb. A comparison of the data suggests some general indicators for the protein-binding specificity of supramolecular anions. Differences in binding were observed between the cavity-containing and planar ligands. The former had a preference for the arginine-rich, flexible C terminus of HUb.
authors.affiliation: School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Mallon
authors.affiliation: Institute for Organic Chemistry, University of Duisburg-Essen, Universitätsstrasse 7, 45117, Essen, Germany.
authors.forename: Som
authors.initials: S
authors.lastname: Dutt
authors.affiliation: Institute for Organic Chemistry, University of Duisburg-Essen, Universitätsstrasse 7, 45117, Essen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schrader
authors.affiliation: School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland. peter.crowley@nuigalway.ie.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Crowley
mesh_terms: D000838:Anions / Q000737:chemistry; D047250:Calixarenes / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D046911:Macromolecular Substances / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010636:Phenols / Q000737:chemistry*; D010712:Phosphatidic Acids / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*; D011721:Pyrenes / Q000737:chemistry*; D025801:Ubiquitin / Q000737:chemistry*
chemical_list: D000838:Anions; D008024:Ligands; D046911:Macromolecular Substances; D010636:Phenols; D010712:Phosphatidic Acids; D011166:Porphyrins; D011721:Pyrenes; D025801:Ubiquitin; C021632:bisphosphatidic acid; C541374:mesotetrakis(sulfonatophenyl)porphyrin; C511968:p-sulfonatocalix(4)arene; D047250:Calixarenes; C041343:1,3,6,8-pyrene tetrasulfonate
keywords: NMR; arginine; calixarenes; lysine; molecular recognition