Metal-binding selectivity and coordination dynamics for cyanobacterial microcystins with Zn, Cu, Fe, Mg, and Ca

Microcystins are toxic cyclic peptides produced worldwide by cyanobacteria in surface caters. The general structure of microcystin is inherently amenable to metal complexation. However, structural characterization of metal–microcystin complexes is lacking. Here we performed molecular dynamics simulations to obtain structures of aqueous complexes of microcystin–leucine–arginine and microcystin–arginine–arginine with Ca²⁺, Mg²⁺, Fe²⁺, Zn²⁺, and Cu²⁺. Results show that complexes with Cu²⁺ and Zn²⁺ were the most stable. Shorter metal-O atom distances result in more favorable complexes. For instance, the relatively stronger Zn–microcystin complexes have metal-O_carboxyl distances of 1.78 Å, whereas the weaker Ca–microcystin complexes have this distance greater than 2.0 Å. Favorable metal complexation is attributed to the conformation of the microcystin peptide cavity that facilitated a specific coordination geometry of carboxyl and keto O atoms around the metal cation. Our findings imply that the cellular and extracellular roles of microcystin with respect to metal chelation are controlled both by the metal species and by the population of microcystin variants.