title: A study of the binding requirements of calyculin A and dephosphonocalyculin A with PP1, development of a molecular recognition model for the binding interactions of the okadaic acid class of compounds with PP1.
abstract: The interactions of the okadaic acid class of compounds, with special emphasis on the solution structures of calyculin A and dephosphonocalyculin A with PP1 are reported. After examination of the interactions of all docked structures, a receptor based pharmacophore model for the interactions of the protein phosphatase inhibitors has been developed. Calyculin A or dephosphonocalyculin A can interact with the enzyme in either a manner similar to the reported crystal structure, or in an extended form. The inhibitors require two essential regions interacting with the hydrophobic region and the central metal binding regions of the enzyme. This simplified model is consistent with previously published models of the okadaic acid class of compounds with PP1.
authors: AstraZeneca R&D, Griffith University, Brisbane 4111, Australia.
authors: K E
authors: KE
authors: Volter
authors: K J
authors: KJ
authors: Embrey
authors: G K
authors: GK
authors: Pierens
authors: R J
authors: RJ
authors: Quinn
mesh_terms: D018360:Crystallography, X-Ray; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006860:Hydrogen Bonding; D008387:Marine Toxins; D052998:Microcystins; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins; D019319:Okadaic Acid / Q000378:metabolism*; D010080:Oxazoles / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D052998:Microcystins; D009419:Nerve Tissue Proteins; D010080:Oxazoles; D010456:Peptides, Cyclic; D010750:Phosphoproteins; C427544:dephosphonocalyculin A; C093605:motuporin; D019319:Okadaic Acid; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; C057862:cyanoginosin LR