Projects per year
Abstract
Lipopolysaccharides are complex molecules found in the cell envelop of many Gram‐negative bacteria. The toxic activity of these molecules has led to the terminology of endotoxins. They provide bacteria with structural integrity and protection from external environmental conditions, and they interact with host signaling receptors to induce host immune responses. Bacteria have evolved enzymes that act to modify lipopolysaccharides, particularly the lipid A region of the molecule, to enable the circumvention of host immune system responses. These modifications include changes to lipopolysaccharide by the addition of positively charged sugars, such as N‐Ara4N, and phosphoethanolamine (pEtN). Other modifications include hydroxylation, acylation, and deacylation of fatty acyl chains. We review the two‐component regulatory mechanisms for enzymes that carry out these modifications and provide details of the structures of four enzymes (PagP, PagL, pEtN transferases, and ArnT) that modify the lipid A portion of lipopolysaccharides. We focus largely on the three‐dimensional structures of these enzymes, which provide an understanding of how their substrate binding and catalytic activities are mediated. A structure–function–based understanding of these enzymes provides a platform for the development of novel therapeutics to treat antibiotic resistance.
Original language | English |
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Pages (from-to) | 19-37 |
Number of pages | 19 |
Journal | Annals of the New York Academy of Sciences |
Volume | 1459 |
Issue number | 1 |
Early online date | 25 Sep 2019 |
DOIs | |
Publication status | Published - 1 Jan 2020 |
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Dive into the research topics of 'Structure and function of lipid A-modifying enzymes'. Together they form a unique fingerprint.Projects
- 1 Finished
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Structure-based design of novel therapeutics for multi-drug resistant Neisseria gonorrhoeae
Vrielink, A., Stubbs, K., Scanlon, M. & Kahler, C.
National Health & Medical Research Council NHMRC
1/01/15 → 31/12/19
Project: Research