6MK8

NMR structure of Database designed and improved anti-Staphylococcal peptide DFT503 bound to micelles

Summary for 6MK8

• Entry DOI: 10.2210/pdb6mk8/pdb
• NMR Information: BMRB: 30524
• Descriptor: Anti-Staphylococcal peptide DFT503 (1 entity in total)
• Functional Keywords: antimicrobial peptides, amphipathic helix, leucine-rich peptides, database designed peptides, antimicrobial protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 1338.72

Authors

Wang, G. (deposition date: 2018-09-25, release date: 2019-06-19, Last modification date: 2024-10-16)

Primary citation

Mishra, B.,Lakshmaiah Narayana, J.,Lushnikova, T.,Wang, X.,Wang, G.
Low cationicity is important for systemic in vivo efficacy of database-derived peptides against drug-resistant Gram-positive pathogens.
Proc.Natl.Acad.Sci.USA, 116:13517-13522, 2019

PubMed Abstract: As bacterial resistance to traditional antibiotics continues to emerge, new alternatives are urgently needed. Antimicrobial peptides (AMPs) are important candidates. However, how AMPs are designed with in vivo efficacy is poorly understood. Our study was designed to understand structural moieties of cationic peptides that would lead to their successful use as antibacterial agents. In contrast to the common perception, serum binding and peptide stability were not the major reasons for in vivo failure in our studies. Rather, our systematic study of a series of peptides with varying lysines revealed the significance of low cationicity for systemic in vivo efficacy against Gram-positive pathogens. We propose that peptides with biased amino acid compositions are not favored to associate with multiple host factors and are more likely to show in vivo efficacy. Thus, our results uncover a useful design strategy for developing potent peptides against multidrug-resistant pathogens.

PubMed: 31209048
DOI: 10.1073/pnas.1821410116

Experimental method

SOLUTION NMR