Belizeanic acid: a potent protein phosphatase 1 inhibitor belonging to the okadaic acid class, with an unusual skeleton.
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.
Cruz
Patricia G
PG
Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Av. Astrofísico Francisco Sánchez 2, La Laguna, Tenerife, Spain.
Fernández
José Javier
JJ
Norte
Manuel
M
Daranas
Antonio Hernández
AH
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
D004791:Enzyme Inhibitors; C532000:belizeanic acid; D019319:Okadaic Acid; D054645:Protein Phosphatase 1