A Molecular Basis for Different Interactions of Marine Toxins with Protein Phosphatase-1

Quantitatively evaluating detoxification of the hepatotoxic microcystins through the glutathione and cysteine pathway in the cyanobacteria-eating bighead carp

“…Hodgson (2004) in their book, mentioned that there is not a separate pathway for the two derivatives (MC-GSH and MC-Cys), but a difference in the toxicokinetics, and our study showed that the pathways also differ. Bagu et al (1997) confirmed that the inhibition of protein phosphatases 1 and 2A for MCs is through binding covalently with the Cys-273 of the PP-1 and 2A. Based on the above comments together with the present results, we speculate that a different detoxification pathway exists in aquatic animals: MC-LR and MC-RR firstly conjugate with polypeptides or proteins (mainly PP-1 and 2A) containing Cys residues, subsequently, MCLR/RR-Cys is degraded from these polypeptide or protein, and finally is excreted in the form of MCLR/RR-Cys mainly from kidney.…”

Molecular mechanisms underlying inhibition of protein phosphatases by marine toxins

“…It has been hypothesized that hydrophobic interactions may be a significant factor in the tight-binding affinity of the marine toxins for PP-1c (98). Our laboratory has therefore examined the role of hydrophobic interactions between the Adda sidechain of microcytsin-LR and the hydophobic groove of PP-1c in marine toxin potency.…”

Mechanisms of Microcystin-induced Cytotoxicity and Apoptosis

“…Because hydrophobicity may be the initial driving force behind the binding of MC-LR to PP1c, Adda could be responsible for anchoring the cyclic backbone ring into its bound position. The other contributing residues for inhibition, Asp and Glu, have D-oriented, negatively charged carboxyl groups located underneath the saddle which are both oriented to interact with positively charged Arg-96 of PP1c [41,42]. Finally, the secondary covalent linkage that forms after inhibition is dependent on the modified amino acid Mdha being located at the front and top of the toxin saddle to link covalently to Cys-273 [43].…”