Structure and function of lipid A-modifying enzymes

Anandhi Anandan, Alice Vrielink

Research output: Contribution to journalReview article

6 Citations (Scopus)
334 Downloads (Pure)

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 languageEnglish
Pages (from-to)19-37
JournalAnnals of the New York Academy of Sciences
Volume1459
Issue number1
Early online date25 Sep 2019
DOIs
Publication statusPublished - Jan 2020

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