8HVS

Solution Structure of the Antimicrobial Peptide HT-2

Summary for 8HVS

• Entry DOI: 10.2210/pdb8hvs/pdb
• Descriptor: ARG-PHE-LEU-ARG-ARG-ILE-PHE-PHE-PHE-PHE (1 entity in total)
• Functional Keywords: structure from cyana 2.1, antibiotic
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 1451.78

Authors

Li, S.,Yang, A. (deposition date: 2022-12-27, release date: 2023-10-25, Last modification date: 2024-05-15)

Primary citation

Tang, Z.,Jiang, W.,Li, S.,Huang, X.,Yang, Y.,Chen, X.,Qiu, J.,Xiao, C.,Xie, Y.,Zhang, X.,Li, J.,Verma, C.S.,He, Y.,Yang, A.
Design and evaluation of tadpole-like conformational antimicrobial peptides.
Commun Biol, 6:1177-1177, 2023

PubMed Abstract: Antimicrobial peptides are promising alternatives to conventional antibiotics. Herein, we report a class of "tadpole-like" peptides consisting of an amphipathic α-helical head and an aromatic tail. A structure-activity relationship (SAR) study of "tadpole-like" temporin-SHf and its analogs revealed that increasing the number of aromatic residues in the tail, introducing Arg to the α-helical head and rearranging the peptide topology dramatically increased antimicrobial activity. Through progressive structural optimization, we obtained two peptides, HT2 and RI-HT2, which exhibited potent antimicrobial activity, no hemolytic activity and cytotoxicity, and no propensity to induce resistance. NMR and molecular dynamics simulations revealed that both peptides indeed adopted "tadpole-like" conformations. Fluorescence experiments and electron microscopy confirmed the membrane targeting mechanisms of the peptides. Our studies not only lead to the discovery of a series of ultrashort peptides with potent broad-spectrum antimicrobial activities, but also provide a new strategy for rational design of novel "tadpole-like" antimicrobial peptides.

PubMed: 37980400
DOI: 10.1038/s42003-023-05560-0

Experimental method

SOLUTION NMR