title: Self-association of okadaic acid: structural and pharmacological significance.
abstract: Okadaic acid (OA) has been an invaluable pharmacological tool in the study of cellular signaling. The great affinity of this polyether for its targets together with its high specificity to inhibit certain protein phosphatases enables the differential study of these proteins. Crystallographic structures of protein phosphatases in complex with OA show a 1:1 protein to toxin ratio. Nevertheless, it has been found that OA is able to self-associate under certain conditions although very little is known about the importance of this phenomenon. Here we review the available knowledge on the latter topic and we report on the existence of an unusual self-associated tetrameric form. The structure of these oligomers is proposed based on spectroscopic data and molecular modeling calculations.
authors.affiliation: University Institute for Bio-Organic Chemistry "Antonio González"-IUBO, University of La Laguna-ULL, Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Cruz
authors.forename: Manuel
authors.initials: M
authors.lastname: Norte
authors.forename: Alberto Hernández
authors.initials: AH
authors.lastname: Creus
authors.forename: José J
authors.initials: JJ
authors.lastname: Fernández
authors.forename: Antonio Hernández
authors.initials: AH
authors.lastname: Daranas
mesh_terms: D003461:Crystallography; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D019319:Okadaic Acid / Q000737:chemistry* / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013057:Spectrum Analysis
chemical_list: D004791:Enzyme Inhibitors; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases