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Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli
Most Gram-negative bacteria are surrounded by a glycolipid called lipopolysaccharide (LPS), which forms a barrier to hydrophobic toxins and, in pathogenic bacteria, is a virulence factor. During LPS biosynthesis, a membrane-associated glycosyltransferase (LpxB) forms a tetra-acylated disaccharide th...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785501/ https://www.ncbi.nlm.nih.gov/pubmed/29371662 http://dx.doi.org/10.1038/s41467-017-02712-9 |
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author | Bohl, Heather O. Shi, Ke Lee, John K. Aihara, Hideki |
author_facet | Bohl, Heather O. Shi, Ke Lee, John K. Aihara, Hideki |
author_sort | Bohl, Heather O. |
collection | PubMed |
description | Most Gram-negative bacteria are surrounded by a glycolipid called lipopolysaccharide (LPS), which forms a barrier to hydrophobic toxins and, in pathogenic bacteria, is a virulence factor. During LPS biosynthesis, a membrane-associated glycosyltransferase (LpxB) forms a tetra-acylated disaccharide that is further acylated to form the membrane anchor moiety of LPS. Here we solve the structure of a soluble and catalytically competent LpxB by X-ray crystallography. The structure reveals that LpxB has a glycosyltransferase-B family fold but with a highly intertwined, C-terminally swapped dimer comprising four domains. We identify key catalytic residues with a product, UDP, bound in the active site, as well as clusters of hydrophobic residues that likely mediate productive membrane association or capture of lipidic substrates. These studies provide the basis for rational design of antibiotics targeting a crucial step in LPS biosynthesis. |
format | Online Article Text |
id | pubmed-5785501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57855012018-01-29 Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli Bohl, Heather O. Shi, Ke Lee, John K. Aihara, Hideki Nat Commun Article Most Gram-negative bacteria are surrounded by a glycolipid called lipopolysaccharide (LPS), which forms a barrier to hydrophobic toxins and, in pathogenic bacteria, is a virulence factor. During LPS biosynthesis, a membrane-associated glycosyltransferase (LpxB) forms a tetra-acylated disaccharide that is further acylated to form the membrane anchor moiety of LPS. Here we solve the structure of a soluble and catalytically competent LpxB by X-ray crystallography. The structure reveals that LpxB has a glycosyltransferase-B family fold but with a highly intertwined, C-terminally swapped dimer comprising four domains. We identify key catalytic residues with a product, UDP, bound in the active site, as well as clusters of hydrophobic residues that likely mediate productive membrane association or capture of lipidic substrates. These studies provide the basis for rational design of antibiotics targeting a crucial step in LPS biosynthesis. Nature Publishing Group UK 2018-01-25 /pmc/articles/PMC5785501/ /pubmed/29371662 http://dx.doi.org/10.1038/s41467-017-02712-9 Text en © The Author(s) 2018 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Bohl, Heather O. Shi, Ke Lee, John K. Aihara, Hideki Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli |
title | Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli |
title_full | Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli |
title_fullStr | Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli |
title_full_unstemmed | Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli |
title_short | Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli |
title_sort | crystal structure of lipid a disaccharide synthase lpxb from escherichia coli |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785501/ https://www.ncbi.nlm.nih.gov/pubmed/29371662 http://dx.doi.org/10.1038/s41467-017-02712-9 |
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