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Data for Structural studies suggest aggregation as one of the modes of action for teixobactin
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Öster, Carl, Walkowiak, Grzegorz P., Hughes, Dallas E., Spoering, Amy L., Peoples, Aaron J., Catherwood, Anita C., Tod, Julie A., Lloyd, Adrian J., Herrmann, Torsten, Lewis, Kim, Dowson, Christopher G. and Lewandowski, Józef R. (2018) Data for Structural studies suggest aggregation as one of the modes of action for teixobactin. [Dataset]
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Official URL: http://wrap.warwick.ac.uk/108554
Abstract
Teixobactin is a new promising antibiotic that targets cell wall biosynthesis by binding to lipid II and has no detectable resistance thanks to its unique but yet not fully understood mechanism of operation. To aid in structure-based design of teixobactin analogues with improved pharmacological properties, we present a 3D structure of native teixobactin in membrane mimetics and characterise its binding to lipid II through a combination of solution NMR and fast (90 kHz) magic angle spinning solid state NMR. In NMR titrations, we observe a pattern strongly suggesting interactions between the backbone of the C-terminal “cage” with the pyrophosphate moiety in lipid II. We find that the N-terminal part of teixobactin does not only act as a membrane anchor, as previously thought, but is actively involved in binding. Moreover, teixobactin forms a well-structured and specific complex with lipid II, where the N-terminal part of teixobactin assumes a β conformation that is highly prone to aggregation, which likely contributes to the antibiotic’s high bactericidal efficiency. Overall, our study provides several new clues to teixobactin’s modes of action.
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| Subjects: | Q Science > QD Chemistry Q Science > QR Microbiology R Medicine > RM Therapeutics. Pharmacology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) |
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| Type of Data: | Zipped raw NMR data in Bruker format | ||||||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Antibiotics, Biosynthesis, Lipids, Nuclear magnetic resonance, Drug resistance in microorganisms | ||||||||||||||||||||||||||||||
| Publisher: | University of Warwick, Department of Chemistry | ||||||||||||||||||||||||||||||
| Official Date: | 19 September 2018 | ||||||||||||||||||||||||||||||
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| Status: | Not Peer Reviewed | ||||||||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||
| Copyright Holders: | University of Warwick | ||||||||||||||||||||||||||||||
| Description: | The data directories contain raw NMR data used in the Oster et al. Chemical Science manuscript entitled “Structural studies suggest aggregation as one of the modes of action for teixobactin”. The directory called “solid-state” contains solid state NMR data on a sedimented complex of [U-13C,15N]teixobactin with Gram-negative lipid II in DPC micelles. The directory called “solution-state” contains solution NMR data on various samples. 13C15N_txb_aq - indicates data on a saturated aqueous solution of [U-13C,15N]teixobactin 13C15N_txb_dpc - indicated data on [U-13C,15N]teixobactin in DPC micelles 13C15N_txb_dpc_l2 - indicates data on [U-13C,15N]teixobactin in DPC micelles in a presence of Gram-negative lipid II 13C15N_txb_l2 - indicates data on [U-13C,15N]teixobactin in a presence of Gram-positive lipid II in aqueous solution For the detailed information on conditions, please, refer to the manuscript. |
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| Date of first compliant deposit: | 21 September 2018 | ||||||||||||||||||||||||||||||
| Date of first compliant Open Access: | 1 October 2018 | ||||||||||||||||||||||||||||||
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