title: Solution structures of cyclosporin a and its complex with dysprosium(III) in SDS micelles: NMR and molecular dynamics studies.
abstract: Cyclosporin A (CsA) is a cyclic naturally occurring peptide used to prevent graft rejection in organ transplantations. Its immunosuppressive activity is due to the formation of a complex with cyclophilin A (Cyp), in which the cis 9MeLeu-10MeLeu amide bond of CsA assumes a trans conformation. The mechanism of the conformational inversion has not been delineated, but it has been postulated that metal ions binding induces a conformational change that enables CsA to bind Cyp. In this work, we solved the structures of CsA in sodium dodecyl sulfate (SDS) micelles (which enhance its solubility and mimic the hydrophobic environment clinically used for drug delivery) and its complex with Dy(III) ion, whose coordination chemistry is frequently used to reproduce the effect of Ca(II). The paramagnetic properties of Dy(III) allowed us to build up a structure using proton relaxation enhancements, which remains stable in a MD simulation in the micelle environment.
authors: Department of Chemistry and the NMR Center, University of Siena, Via A. Moro, 53100 Siena, Italy.
authors: Francesca
authors: F
authors: Bernardi
authors: Nicola
authors: N
authors: D'Amelio
authors: Elena
authors: E
authors: Gaggelli
authors: Elena
authors: E
authors: Molteni
authors: Gianni
authors: G
authors: Valensin
mesh_terms: D000577:Amides / Q000737:chemistry; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry; D002412:Cations; D003198:Computer Simulation; D016572:Cyclosporine / Q000737:chemistry*; D004419:Dysprosium / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007166:Immunosuppressive Agents / Q000737:chemistry*; D007536:Isomerism; D007930:Leucine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008823:Micelles; D008958:Models, Molecular; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry
chemical_list: D000577:Amides; D002412:Cations; D007166:Immunosuppressive Agents; D008823:Micelles; D012996:Solutions; D004419:Dysprosium; D012967:Sodium Dodecyl Sulfate; D016572:Cyclosporine; D007930:Leucine; D002118:Calcium