Investigation of microcystin conformation and binding towards PPP1 by molecular dynamics simulation.
Chem Biol Interact
; 351: 109766, 2022 Jan 05.
Article
en En
| MEDLINE
| ID: mdl-34861245
ABSTRACT
Microcystins (MC) are a group of structurally similar cyanotoxins with currently 279 described structural variants. Human exposure is frequent by consumption of contaminated water, food or food supplements. MC can result in serious intoxications, commensurate with ensuing pathology in various organs or in rare cases even mortality. The current WHO risk assessment primarily considers MC-LR, while all other structural variants are treated as equivalent to MC-LR, despite that current data strongly suggest that MC-LR is not the most toxic MC, and toxicity can be very different for MC congeners. To investigate and analyse binding and conformation of different MC congeners, we applied for the first time Molecular Dynamics (MD) simulation to four MC congeners (MC-LR, MC-LF, [Enantio-Adda5]MC-LF, [ß-D-Asp3,Dhb7]MC-RR). We could show that ser/thr protein phosphatase 1 is stable in all MD simulations and that MC-LR backbone adopts to a second conformation in solvent MD simulation, which was previously unknown. We could also show that MC congeners can adopt to different backbone conformation when simulated in solvent or in complex with ser/thr protein phosphatase 1 and differ in their binding behaviour. Our findings suggest that MD Simulation of different MC congeners aid in understanding structural differences and binding of this group of structurally similar cyanotoxins.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Microcistinas
/
Proteína Fosfatasa 1
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Año:
2022
Tipo del documento:
Article