Polyamines: naturally occurring small molecule modulators of electrostatic protein-protein interactions.

摘要: Abstract Modulations of protein–protein interactions are a key step in regulating protein function, especially networks. Modulators these supposed to be candidates for the development novel drugs. Here, we describe role small, polycationic and highly abundant natural polyamines that could efficiently bind charged spots at interfaces as modulators such interactions. Using mitochondrial cytochrome P45011A1 (CYP11A1) electron transfer system model, have analyzed capability putrescine, spermidine, spermine physiologically relevant concentrations affect between adrenodoxin reductase (AdR), (Adx), CYP11A1. The actions on individual components, their association/dissociation, transfer, substrate conversion were examined. These studies revealed modulating effects distinct entire complex way. Modulation via changed appeared plausible from docking experiments suggested favourable high-affinity binding sites (spermine > spermidine > putrescine) AdR–Adx interface. Our findings imply first time small endogenous compounds capable interfering with components transient complexes might control functions by electrostatic