@article {3851, title = {Ferintoic acids A and B, new cyclic hexapeptides from the freshwater cyanobacterium Microcystis aeruginosa}, journal = {Journal of Natural Products}, volume = {59}, number = {6}, year = {1996}, note = {ISI Document Delivery No.: UT658Times Cited: 23Cited Reference Count: 30}, month = {Jun}, pages = {570-575}, type = {Article}, abstract = {The cyclic hexapeptides ferintoic acids A (1) and B (2) have been isolated from cells of Microcystis aeruginosa harvested during a natural bloom of the toxic cyanobacterium. The structures of 1 and 2 were determined by a combination of spectroscopic analysis and chemical degradation.}, keywords = {AMINO-ACIDS, BLUE-GREEN-ALGA, INHIBITOR, LR, PEPTIDE, PHASE, PROTEIN PHOSPHATASES, SPONGE THEONELLA SP, TOXIN}, isbn = {0163-3864}, url = {://A1996UT65800004}, author = {Williams, D. E. and Craig, M. and Holmes, C. F. B. and Andersen, R. J.} } @article {3640, title = {Molecular mechanisms underlying the interaction of motuporin and microycystins with type-1 and type-2A protein phosphatases}, journal = {Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire}, volume = {74}, number = {4}, year = {1996}, note = {ISI Document Delivery No.: VX367Times Cited: 61Cited Reference Count: 35}, pages = {569-578}, type = {Article}, abstract = {Heptapeptide microcystin and pentapeptide motuporin (nodularin-V) are equipotent inhibitors of type-1 and type-2A protein phosphatase catalytic subunits (PP-1c and PP-2Ac). Herein we describe elucidation of the molecular mechanisms involved in the interaction of these structurally similar hepatotoxins with PP-1c/PP-2Ac and identification of an important functional difference between their mode of interaction with these enzymes. Microcystin-LR, microcystin-LA and microcystin-LL were found to interact with PP-2Ac and PP-1c by a two-step mechanism involving rapid binding and inactivation of the protein phosphatase (PPase) catalytic subunit, followed by a slower covalent interaction (within hours). Covalent adducts comprising PPase-toxin complexes were separated from free PPase by C-18 reverse-phase liquid chromatography, thus allowing the time course of covalent adduct formation to be quantitated. In contrast to microcystins, motuporin (nodularin-V) and nodularin-R were unable to form covalent complexes with either PP-1c or PP-2Ac even after 96 h incubation. Specific reduction of microcystin-LA to dihydromicrocystin-LA abolished the ability of the toxin to form a covalent adduct with PP-2Ac. Specific methyl esterification of the single Glu residue in microcystin-LR rendered this toxin inactive as a PPase inhibitor and abolished subsequent formation of a covalent adduct. Our data indicate that inactivation of PP-2Ac/PP-1c by microcystins precedes covalent modification of the PPases via a Michael addition reaction between a nucleophilic phosphatase residue and Mdha in the heptapeptide toxin. In contrast, following rapid inactivation of PP-2Ac/PP-1c by motuporin, the equivalent N-methyldehydrobutyrine residue in this toxin is unreactive and does not form a covalent bond with the PPases. These results are consistent with structural data for (i) the NMR solution structures of microcystin-LR and motuporin, which indicate a striking difference in the relative positions of their corresponding dehydroamino acids in the toxin peptide backbone, and (ii) X-ray crystallographic data on an inactive complex between PP-1c and microcystin-LR, which show a covalent bond between Cys-273 and the bound toxin.}, keywords = {BLUE-GREEN-ALGAE, CATALYTIC SUBUNIT, cyanobacteria, IDENTIFICATION, MICROCYSTIN-LR, microcystins, motuporin, nodularin, OKADAIC ACID, PHOSPHORYLATION, POTENT INHIBITOR, PROTEIN, PROTEIN PHOSPHATASES, RAT-LIVER, TOXINS}, isbn = {0829-8211}, url = {://A1996VX36700017}, author = {Craig, M. and Luu, H. A. and McCready, T. L. and Williams, D. and Andersen, R. J. and Holmes, C. F. B.} } @article {3234, title = {COMPARISON OF THE SOLUTION STRUCTURES OF MICROCYSTIN-LR AND MOTUPORIN}, journal = {Nature Structural Biology}, volume = {2}, number = {2}, year = {1995}, note = {ISI Document Delivery No.: RF665Times Cited: 1Cited Reference Count: 15}, month = {Feb}, pages = {114-116}, type = {Letter}, abstract = {A comparison of the structures of two cyanobacterial toxins yields insights into how they may inhibit protein phosphatase-1 and -2A and why microcystins but not motuporin may covalently modify their protein phosphatase targets.}, keywords = {INHIBITOR, nodularin, POTENT, PROTEIN PHOSPHATASES, TOXINS}, isbn = {1072-8368}, url = {://A1995RF66500006}, author = {Bagy, J. R. and Sonnichsen, F. D. and Williams, D. and Andersen, R. J. and Sykes, B. D. and Holmes, C. F. B.} }