Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 19-37 |
| Journal | Annals of the New York Academy of Sciences |
| Volume | 1459 |
| Issue number | 1 |
| Early online date | 25 Sep 2019 |
| DOIs | |
| Publication status | Published - Jan 2020 |
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Structure and function of lipid A-modifying enzymes. / Anandan, Anandhi; Vrielink, Alice.
In: Annals of the New York Academy of Sciences, Vol. 1459, No. 1, 01.2020, p. 19-37.Research output: Contribution to journal › Review article
TY - JOUR
T1 - Structure and function of lipid A-modifying enzymes
AU - Anandan, Anandhi
AU - Vrielink, Alice
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
U2 - 10.1111/nyas.14244
DO - 10.1111/nyas.14244
M3 - Review article
VL - 1459
SP - 19
EP - 37
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
SN - 0077-8923
IS - 1
ER -