Structural investigation of syringomycin-E using molecular dynamics simulation and NMR

Area of Science:

• Biochemistry
• Microbiology
• Structural Biology

Background:

• Syringomycin-E (SR-E) is a cyclic lipodepsinonapeptide from Pseudomonas syringae pv. syringae.
• SR-E exhibits antifungal activity, targeting microbial plasma membranes by forming channels.
• The high-resolution structure of SR-E and its channel formation mechanism remain largely unknown.

Purpose of the Study:

• To elucidate the atomic-level molecular features of Syringomycin-E (SR-E) in aqueous and lipid environments.
• To provide atomistic models of SR-E structure relevant to its biological function.
• To advance the understanding of SR-E's antifungal and antibacterial mechanisms.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy to study SR-E in water.
• Molecular Dynamics (MD) simulations (200 ns) of SR-E in water and octane.
• Integration of NMR NOE data as distance restraints in MD simulations.

Main Results:

• MD simulations generated atomistic models of SR-E structure.
• Simulated structures showed good agreement with experimental NMR NOE and circular dichroism data.
• The study provides detailed insights into SR-E's conformation in different environments.

Conclusions:

• The study provides validated atomistic models of Syringomycin-E.
• These models are crucial for understanding SR-E's interaction with plasma membranes.
• This research is a significant step towards comprehending SR-E's antimicrobial activities.