title: Type AII lantibiotic bovicin HJ50 with a rare disulfide bond: structure, structure-activity relationships and mode of action.
abstract: Lantibiotics are ribosomally synthesized antimicrobial peptides containing unusual amino acids. As promising alternatives to conventional antibiotics, they have a high potential for alleviating the problem of emergent antibiotic resistance, with possible applications in many industries that have antibacterial demand. Bovicin HJ50 is a type AII lantibiotic, the largest group of lantibiotics, comprising a linear N-terminal region and a globular C-terminal region. Interestingly, bovicin H50 has a disulfide bond that is rare in this group. Owing to limited information about the spatial structures of type AII lantibiotics, the functional regions of this type and the role of the disulfide bond are still unknown. In the present study, we resolved the solution structure of bovicin HJ50 using NMR spectroscopy. This is the first spatial structure of a type AII lantibiotic. Bovicin HJ50 exhibited high flexibility in aqueous solution, whereas varied rigidities were observed in the different rings with the conserved ring A being the most rigid. The charged residues Lys¹¹, Asp¹² and Lys³⁰, as well as the essential disulfide bond were critical for antimicrobial activity. Importantly, bovicin HJ50 showed not only peptidoglycan precursor lipid II-binding ability, but also pore-forming activity, which is significantly different from other bacteriostatic type AII lantibiotics, suggesting a novel antimicrobial mechanism.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: ‡National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Yingang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: *State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Kunling
authors.initials: K
authors.lastname: Teng
authors.affiliation: *State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Yuheng
authors.initials: Y
authors.lastname: Lin
authors.affiliation: *State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: ‡National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: *State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhong
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001224:Aspartic Acid / Q000737:chemistry; D001430:Bacteriocins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D017124:Conserved Sequence; D003553:Cystine / Q000737:chemistry; D016983:Enterococcus / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D008564:Membrane Potentials / Q000187:drug effects; D016982:Micrococcus luteus / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D016415:Sequence Alignment; D012995:Solubility; D013329:Structure-Activity Relationship; D013499:Surface Properties / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D008081:Liposomes; D050505:Mutant Proteins; D011498:Protein Precursors; D011994:Recombinant Proteins; C000591653:bovicin HJ50, Streptococcus bovis; D001224:Aspartic Acid; D003553:Cystine; D008239:Lysine