Elucidating binding modes of zuonin A enantiomers to JNK1 via in silico methods.

ABSTRACT: Aberrant c-Jun N-terminal kinase (JNK) signaling is associated with a number of diseases, including neurological conditions and cancer. Enantiomers of the lignan zuonin A, (-)-zuonin A and (+)-zuonin A bind isoforms of JNK with similar affinity and disrupt protein-protein interactions at JNK's D-recruitment site. Thus, they are of interest as lead non-ATP competitive inhibitors of the JNKs. While (-)-zuonin A inhibits the activity of JNK toward c-Jun by 80% when saturating, (+)-zuonin A only inhibits by 15%. Molecular docking and molecular dynamics simulations were performed to gain a better understanding of how these inhibitors interact with JNK. The results of this study provide new insight into potential binding modes for (-)-zuonin A and suggest that (-)-zuonin A interacts with JNK via

SUBMITTER: Dykstra DW 

PROVIDER: S-EPMC3804409 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature