title: NMR determination of the bioactive conformation of peloruside A bound to microtubules.
abstract: We report here on the determination of the conformation of Peloruside A bound to biochemically stabilized microtubules, by using TR-NOESY NMR experiments. As a previous step, the conformation of the free molecule in water solution has also been deduced. Despite the large size of the ring, Peloruside A mainly adopts two conformations in water solution. A conformational selection process takes place, and the microtubules-bound conformer is one of those present in the water solution, different than that existing in chloroform medium. A model of the binding mode to tubulin has also been proposed, by docking the bioactive conformation of peloruside, which involves the alpha-tubulin monomer, in contrast with taxol, which binds to the beta-monomer.
authors.affiliation: Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain. jbarbero@cib.csic.es
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.forename: Angeles
authors.initials: A
authors.lastname: Canales
authors.forename: Peter T
authors.initials: PT
authors.lastname: Northcote
authors.forename: Rubén M
authors.initials: RM
authors.lastname: Buey
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Andreu
authors.forename: J Fernando
authors.initials: JF
authors.lastname: Díaz
mesh_terms: D001665:Binding Sites; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000032:analysis / Q000737:chemistry*; D007783:Lactones / Q000032:analysis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008870:Microtubules / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D017434:Protein Structure, Tertiary; D012680:Sensitivity and Specificity; D012996:Solutions / Q000737:chemistry; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D007783:Lactones; D012996:Solutions; C414085:peloruside A; D014867:Water