9ILX
Thanatin VF16QK in complex with LPS
Summary for 9ILX
| Entry DOI | 10.2210/pdb9ilx/pdb |
| Descriptor | VAL-PRO-ILE-ILE-TYR-CYS-ASN-ARG-ARG-THR-DLY-LYS-CYS-LYS-ARG-PHE (1 entity in total) |
| Functional Keywords | structure from cyana 2.1, antibiotic |
| Biological source | Podisus maculiventris |
| Total number of polymer chains | 1 |
| Total formula weight | 2030.53 |
| Authors | |
| Primary citation | Abdullah, S.J.,Guan, J.S.,Mu, Y.,Bhattacharjya, S. Single Disulfide Bond in Host Defense Thanatin Analog Peptides: Antimicrobial Activity, Atomic-Resolution Structures and Target Interactions. Int J Mol Sci, 26:-, 2024 Cited by PubMed Abstract: Host defense antimicrobial peptides (AMPs) are promising lead molecules with which to develop antibiotics against drug-resistant bacterial pathogens. Thanatin, an inducible antimicrobial peptide involved in the host defense of insects, is gaining considerable attention in the generation of novel classes of antibiotics. Thanatin or thanatin-based analog peptides are extremely potent in killing bacterial pathogens in the Enterobacteriaceae family, including drug-resistant strains of and . A single disulfide bond that covalently links two anti-parallel β-strands in thanatin could be pivotal to its selective antibacterial activity and mode of action. However, potential correlations of the disulfide covalent bond with structure, activity and target binding in thanatin peptides are currently unclear to. Here, we examined a 16-residue designed thanatin peptide, namely disulfide-bonded VF16QK, and its Cys to Ser substituted variant, VF16QK, to delineate their structure-activity relationships. Bacterial growth inhibitory activity was only detected for the disulfide-bonded VF16QK peptide. Mechanistically, both peptides vastly differ in their bacterial cell permeabilizations, atomic-resolution structures, interactions with the LPS-outer membrane and target periplasmic protein LptA binding. In particular, analysis of the 3-D structures of the two peptides revealed an altered folded conformation for the VF16QK peptide that was correlated with diminished LPS-outer membrane permeabilization and target interactions. Analysis of docked complexes of LPS-thanatin peptides indicated potential structural requirements and conformational adaptation for antimicrobial activity. Collectively, these observations contrast with those for the disulfide-bonded β-hairpin antimicrobial protegrin and tachyplesin peptides, where disulfide bonds are dispensable for activity. We surmise that the atomistic structures and associated molecular interactions presented in this work can be utilized to design novel thanatin-based antibiotics. PubMed: 39795909DOI: 10.3390/ijms26010051 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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