Structure and Substrate Recognition of the Bottromycin Maturation Enzyme BotP.
Chembiochem
; 17(23): 2286-2292, 2016 12 02.
Article
em En
| MEDLINE
| ID: mdl-27653442
ABSTRACT
The bottromycins are a family of highly modified peptide natural products, which display potent antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Bottromycins have recently been shown to be ribosomally synthesized and post-translationally modified peptides (RiPPs). Unique amongst RiPPs, the precursor peptide BotA contains a C-terminal "follower" sequence, rather than the canonical N-terminal "leader" sequence. We report herein the structural and biochemical characterization of BotP, a leucyl-aminopeptidase-like enzyme from the bottromycin pathway. We demonstrate that BotP is responsible for the removal of the N-terminal methionine from the precursor peptide. Determining the crystal structures of both apo BotP and BotP in complex with Mn2+ allowed us to model a BotP/substrate complex and to rationalize substrate recognition. Our data represent the first step towards targeted compound modification to unlock the full antibiotic potential of bottro- mycin.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucil Aminopeptidase
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article