Structural Insights into Pseudomonas aeruginosa Exotoxin A-Elongation Factor 2 Interactions: A Molecular Dynamics Study.

ABSTRACT: Exotoxin A (ETA) is an extracellular secreted toxin and a single-chain polypeptide with A and B fragments that is produced by Pseudomonas aeruginosa. It catalyzes the ADP-ribosylation of a post-translationally modified histidine (diphthamide) on eukaryotic elongation factor 2 (eEF2), which results in the inactivation of the latter and the inhibition of protein biosynthesis. Studies show that the imidazole ring of diphthamide plays an important role in the ADP-ribosylation catalyzed by the toxin. In this work, we employ different in silico molecular dynamics (MD) simulation approaches to understand the role of diphthamide versus unmodified histidine in eEF2 on the interaction with ETA. Crystal structures of the eEF2-ETA complexes with three different ligands NAD⁺, A

SUBMITTER: Gholami A 

PROVIDER: S-EPMC10015456 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature