5LHK

Bottromycin maturation enzyme BotP in complex with Mn

Summary for 5LHK

• Entry DOI: 10.2210/pdb5lhk/pdb
• Descriptor: Leucine aminopeptidase 2, chloroplastic, MANGANESE (II) ION, BICARBONATE ION, ... (4 entities in total)
• Functional Keywords: botp, bottromycin, ripps, peptidase, hydrolase
• Biological source: Streptomyces sp. BC16019
• Total number of polymer chains: 1
• Total formula weight: 51866.96

Authors

Koehnke, J.,Adam, S. (deposition date: 2016-07-12, release date: 2016-10-05, Last modification date: 2024-05-08)

Primary citation

Mann, G.,Huo, L.,Adam, S.,Nardone, B.,Vendome, J.,Westwood, N.J.,Muller, R.,Koehnke, J.
Structure and Substrate Recognition of the Bottromycin Maturation Enzyme BotP.
Chembiochem, 17:2286-2292, 2016

PubMed 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 Mn 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.

PubMed: 27653442
DOI: 10.1002/cbic.201600406

Experimental method

X-RAY DIFFRACTION (2.32 Å)