1. Investigating the nucleic acid interactions of histone-derived antimicrobial peptides.
- Author
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Sim S, Wang P, Beyer BN, Cutrona KJ, Radhakrishnan ML, and Elmore DE
- Subjects
- Amino Acid Sequence, Amino Acid Substitution, Animals, Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents isolation & purification, Anura physiology, Histones chemical synthesis, Histones isolation & purification, Kinetics, Molecular Dynamics Simulation, Molecular Mimicry, Protein Binding, Protein Structure, Secondary, Proteins chemical synthesis, Proteins isolation & purification, Structure-Activity Relationship, Thermodynamics, Anti-Bacterial Agents chemistry, Arginine chemistry, DNA, Bacterial chemistry, Histones chemistry, Lysine chemistry, Proteins chemistry
- Abstract
While many antimicrobial peptides (AMPs) disrupt bacterial membranes, some translocate into bacteria and interfere with intracellular processes. Buforin II and DesHDAP1 are thought to kill bacteria by interacting with nucleic acids. Here, molecular modeling and experimental measurements are used to show that neither nucleic acid binding peptide selectively binds DNA sequences. Simulations and experiments also show that changing lysines to arginines enhances DNA binding, suggesting that including additional guanidinium groups is a potential strategy to engineer more potent AMPs. Moreover, the lack of binding specificity may make it more difficult for bacteria to evolve resistance to these and other similar AMPs., (© 2017 Federation of European Biochemical Societies.)
- Published
- 2017
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