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Updated: Jun 3, 2025
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Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities
Published on: October 2, 2018
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Single Disulfide Bond in Host Defense Thanatin Analog Peptides: Antimicrobial Activity, Atomic-Resolution Structures
Swaleeha Jaan Abdullah1, Jia Sheng Guan1, Yuguang Mu1
1School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
International Journal of Molecular Sciences
|January 11, 2025
Summary
The disulfide bond in thanatin peptides is crucial for their antibacterial activity against drug-resistant pathogens. This structural feature dictates interactions with bacterial membranes and target proteins, unlike other antimicrobial peptides.
Area of Science:
- Biochemistry
- Structural Biology
- Antimicrobial Peptides
Background:
- Host defense antimicrobial peptides (AMPs) are vital for combating drug-resistant bacteria.
- Thanatin, an insect-derived AMP, shows potent activity against Enterobacteriaceae, including resistant strains.
- The role of thanatin's disulfide bond in its structure-activity relationship remains unclear.
Purpose of the Study:
- To investigate the structure-activity relationships of a designed thanatin peptide (VF16QK) and its disulfide-bond-lacking variant (VF16QKSer).
- To elucidate the mechanism of action and target interactions influenced by the disulfide bond.
Main Methods:
- Comparative analysis of disulfide-bonded (VF16QK) and Cys-to-Ser substituted (VF16QKSer) thanatin peptides.
- Assessment of bacterial growth inhibition and cell permeabilization.
- Determination of atomic-resolution structures and interactions with LPS and LptA.
Main Results:
- Only the disulfide-bonded VF16QK exhibited significant bacterial growth inhibitory activity.
- VF16QKSer showed altered conformation, reduced membrane permeabilization, and diminished target binding compared to VF16QK.
- Disulfide bond is essential for VF16QK's activity, contrasting with other AMPs like protegrin and tachyplesin.
Conclusions:
- The disulfide bond in VF16QK is critical for its antibacterial efficacy, influencing its structure and molecular interactions.
- Understanding these structure-function correlations can guide the design of novel thanatin-based antibiotics.
- The findings highlight a unique mechanism of action for thanatin compared to other disulfide-bonded AMPs.
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