SOLUTION STRUCTURE OF NODULARIN - AN INHIBITOR OF SERINE THREONINE-SPECIFIC PROTEIN PHOSPHATASES/

The three dimensional solution structure of nodularin was studied by N MR and molecular dynamics simulations. The conformation in water was d etermined from the distance and dihedral data by distance geometry and refined by iterative relaxation matrix analysis. The cyclic backbone adopts a well defined conformation but the remote parts of the side ch ains of arginine as well as the amino acid derivative Adda have a larg e spatial dispersion. For the unusual amino acids the partial charges were calculated and nodularin was subjected to molecular dynamic simul ations in water. A good agreement was found between experimental and c omputational data with hydrogen bonds, solvent accessibility, molecula r motion, and conformational exchange. The three-dimensional structure resembles very closely that of microcystin-LR in the chemically equiv alent segment. Therefore, it is expected that the binding of both micr ocystins and nodularins to serine/threonine specific protein phosphata ses is similar on an atomic level.