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

The interactions of the okadaic acid class of compounds, with special empha sis on the solution structures of calyculin A and dephosphonocalyculin A wi th PP1 are reported. After examination of the interactions of all docked st ructures, a receptor based pharmacophore model fur the interactions of the protein phosphatase inhibitors has been developed. Calyculin A or dephospho nocalyculin A can interact with the enzyme in either a manner similar to th e reported crystal structure, or in an extended form. The inhibitors requir e two essential regions interacting with the hydrophobic region and the cen tral metal binding regions of the enzyme. This simplified model is consiste nt with previously published models of the okadaic acid class of compounds with PP1. (C) 2001 Elsevier Science B.V. All rights reserved.