Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL from Pseudomonas aeruginosa.

Proceedings of the National Academy of Sciences of the United States of America
Lucy RuttenJan Tommassen

Abstract

Pathogenic gram-negative bacteria can modify the lipid A portion of their lipopolysaccharide in response to environmental stimuli. 3-O-deacylation of lipid A by the outer membrane enzyme PagL modulates signaling through Toll-like receptor 4, leading to a reduced host immune response. We found that PagL is widely disseminated among gram-negative bacteria. Only four residues are conserved: a Ser, His, Phe, and Asn residue. Here, we describe the crystal structure of PagL from Pseudomonas aeruginosa to 2.0-A resolution. It consists of an eight-stranded beta-barrel with the axis tilted by approximately 30 degrees with respect to the lipid bilayer. The structure reveals that PagL contains an active site with a Ser-His-Glu catalytic triad and an oxyanion hole that comprises the conserved Asn. The importance of active site residues was confirmed in mutagenesis studies. Although PagL is most likely active as a monomer, its active site architecture shows high resemblance to that of the dimeric 12-stranded outer membrane phospholipase A. Modeling of the substrate lipid X onto the active site reveals that the 3-O-acyl chain is accommodated in a hydrophobic groove perpendicular to the membrane plane. In addition, an aspartate makes a hydrog...Continue Reading

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Citations

Sep 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Bing MaChristian R H Raetz
Feb 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Marie RenaultMarc Baldus
Jun 12, 2010·Bioinformatics·Thomas C Freeman, William C Wimley
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Mar 4, 2014·Annual Review of Biochemistry·Chris Whitfield, M Stephen Trent
Oct 10, 2009·Progress in Lipid Research·Xiaoyuan Wang, Peter J Quinn
Jan 29, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lucy RuttenPiet Gros
May 20, 2014·Biological Reviews of the Cambridge Philosophical Society·Xiaoyuan WangAixin Yan
Feb 18, 2014·Current Opinion in Microbiology·Zachary D Dalebroux, Samuel I Miller
Apr 16, 2013·Biochimica Et Biophysica Acta·Christian SohlenkampBrian O Ingram
Dec 18, 2013·Journal of Proteomics·Rachel DuchesneSylvie Chevalier
Dec 23, 2008·Journal of Molecular Biology·Alexander BrosigKay Diederichs
Aug 28, 2009·Innate Immunity·Jerry D KingJoseph S Lam
Oct 27, 2017·FEBS Letters·Robert GustafssonPål Stenmark
Feb 10, 2007·Expert Review of Proteomics·Ildikó KustosFerenc Kilár
Oct 29, 2019·Protein Science : a Publication of the Protein Society·Wei TianJie Liang
Sep 26, 2019·Annals of the New York Academy of Sciences·Anandhi Anandan, Alice Vrielink
Jul 19, 2012·Chembiochem : a European Journal of Chemical Biology·Martina WerneburgJohn A Robinson
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Aug 24, 2017·Journal of Computer-aided Molecular Design·Zeynep KurkcuogluA M J J Bonvin

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