The leader peptide of mutacin 1140 has distinct structural components compared to related class I lantibiotics.
Bottom Line: Mutacin 1140 leader peptide is structurally unique compared to other class I lantibiotic leader peptides.We have also determined that mutacin 1140 leader peptide contains a novel four amino acid motif compared to related lantibiotics.Our study on mutacin 1140 leader peptide provides a basis for future studies aimed at understanding its interaction with the PTM enzymes.
Affiliation: Department of Biological Sciences, Texas A&M University, College Station, Texas, 77843.Show MeSH
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Mentions: Many strains of medically important bacteria have become increasingly resistant to currently available antibiotics. Healthcare-associated infections caused by multi-drug-resistant pathogens are leading to longer hospital stays and increased mortality. Worldwide, millions suffer from antibiotic-resistant infections, which results in a huge cost to the healthcare system. The development of new antibiotics has become a critical, unmet need in the medical community (Talbot et al. 2006; Laible 2014; Lushniak 2014). Lantibiotics are an important class of antibiotics with potential clinical relevance for the treatment of antibiotic-resistant Gram-positive bacteria (Chatterjee et al. 2005; Lubelski et al. 2008; Smith and Hillman 2008; Oman and van der Donk 2010). Lantibiotics acquired their name because of the characteristic lanthionine rings found in the bioactive core peptide. Lantibiotics also contain an array of unusual amino acids such as 2,3-didehydroalanine (Dha), 2, 3-didehydrobutyrine (Dhb), S-amino vinyl-D-cysteine (AviCys), aminobutyrate (Abu), 2-oxopropionyl, 2-oxobutyryl, and hydroxypropionyl (Chatterjee et al. 2005; Lubelski et al. 2008; Smith and Hillman 2008; Oman and van der Donk 2010). The molecular structure of mutacin 1140 contains four macrocyclic rings (see Fig. 1A), each of which contains a lanthionine or methyllanthionine residue. Mutacin 1140 also contains the post translationally modified amino acid residues 2,3-didehydroalanine (Dha), 2, 3-didehydrobutyrine (Dhb), and S-amino vinyl-D-cysteine (AviCys) (Smith et al. 2000, 2003). Mutacin 1140 rings A and B (see Fig. 1A), the lipid II-binding domain, is similar to the class I lantibiotics nisin and epidermin (Smith et al. 2000, 2003). It was discovered that both nisin and mutacin 1140 abduct lipid II from the site of new cell wall synthesis, ultimately causing cell death (Hasper et al. 2006; Smith et al. 2008).
Affiliation: Department of Biological Sciences, Texas A&M University, College Station, Texas, 77843.