title: Belizeanic acid: a potent protein phosphatase 1 inhibitor belonging to the okadaic acid class, with an unusual skeleton.
abstract: Belizeanic acid (BA), a novel metabolite belonging to the okadaic acid class of protein phosphatase inhibitors, was isolated from artificial cultures of the dinoflagellate Prorocentrum belizeanum. The structure and conformational behaviour of BA was elucidated by a combination of NMR spectroscopy and conformational analysis. The isolation of this metabolite, which possesses a simplified version of the okadaic acid skeleton, supports the biogenetic pathway previously reported for this class of compounds. BA showed potent inhibitory activity against protein phosphatase 1 (PP1) within the nM range. A plausible model for the interaction of BA with the PP1 binding pocket was derived from computational docking studies.
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Av. Astrofísico Francisco Sánchez 2, La Laguna, Tenerife, Spain.
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Cruz
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Fernández
authors.forename: Manuel
authors.initials: M
authors.lastname: Norte
authors.forename: Antonio Hernández
authors.initials: AH
authors.lastname: Daranas
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D019319:Okadaic Acid / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D004791:Enzyme Inhibitors; C532000:belizeanic acid; D019319:Okadaic Acid; D054645:Protein Phosphatase 1