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The Lipid A 3-O-deacylase (PagL) Family [Function: Enzyme] Seed alignment | Full alignment | Pfam page | Pfam Wiki page

Members of this family are enzymes catalyzing the removal of the fatty acyl chain from the 3rd position of lipid A, the highly conserved lipid moiety of the lipopolysaccharide (LPS), which is one of the main constituents of the Gram-negative bacterial outer membrane. The first identified member of the family was the outer membrane-localized lipid A 3-O-deacylase, which is encoded by the PagL gene of Salmonella enterica serovar typhimurium. Homologs have been discovered in a variety of Gram-negative bacteria, although the overall sequence similarity is rather low. When expressed in Escherichia coli and upon deacylation by PagL, lipid A underwent another modification, which was the result of the activity of the endogenous palmitoyl-transferase PagP. A conserved histidine-serine couple was identified as the active site suggesting a catalytic mechanism similar to serine hydrolases. The exact biological function of PagL remains unclear, while its high-resolution structure revealed a dimeric structure with ß-barrels comprising 8 transmembrane strands.

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Literature references

Polymyxin-Induced Lipid A Deacylation in Pseudomonas aeruginosa Perturbs Polymyxin Penetration and Confers High-Level Resistance
ACS Chem Biol. 2018 Jan 19;13(1):121-130. doi: 10.1021/acschembio.7b00836. Epub 2017 Dec 11.
PMID: 29182311

The LpxL acyltransferase is required for normal growth and penta-acylation of lipid A in Burkholderia cenocepacia
Mol Microbiol. 2017 Apr;104(1):144-162. doi: 10.1111/mmi.13618. Epub 2017 Jan 27.
PMID: 28085228

Meningococcal Outer Membrane Vesicle Composition-Dependent Activation of the Innate Immune Response
Infect Immun. 2016 Sep 19;84(10):3024-33. doi: 10.1128/IAI.00635-16. Print 2016 Oct.
PMID: 27481244

LPS Remodeling Triggers Formation of Outer Membrane Vesicles in Salmonella
mBio. 2016 Jul 12;7(4):e00940-16. doi: 10.1128/mBio.00940-16.
PMID: 27406567

Immunological evaluation of OMV(PagL)+Bap(1-487aa) and AbOmpA(8-346aa)+Bap(1-487aa) as vaccine candidates against Acinetobacter baumannii sepsis infection
Mol Immunol. 2015 Oct;67(2 Pt B):552-8. doi: 10.1016/j.molimm.2015.07.031. Epub 2015 Aug 12.
PMID: 26277277

Heterologous expression of 3-O-deacylase in Acinetobacter baumannii modulates the endotoxicity of lipopolysaccharide
J Mol Microbiol Biotechnol. 2015;25(1):37-44. doi: 10.1159/000371815. Epub 2015 Feb 13.
PMID: 25677974

Acellular pertussis vaccine based on outer membrane vesicles capable of conferring both long-lasting immunity and protection against different strain genotypes
Vaccine. 2014 Feb 12;32(8):931-7. doi: 10.1016/j.vaccine.2013.12.048. Epub 2014 Jan 4.
PMID: 24397896

Elucidation of the 3-O-deacylase gene, pagL, required for the removal of primary ß-hydroxy fatty acid from the lipid A in the nitrogen-fixing endosymbiont Rhizobium etli CE3
J Biol Chem. 2013 Apr 26;288(17):12004-13. doi: 10.1074/jbc.M113.470484. Epub 2013 Mar 19.
PMID: 23511636

Palmitoylation state impacts induction of innate and acquired immunity by the Salmonella enterica serovar typhimurium msbB mutant
Infect Immun. 2011 Dec;79(12):5027-38. doi: 10.1128/IAI.05524-11. Epub 2011 Sep 19.
PMID: 21930761

Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate
Vaccine. 2011 Feb 11;29(8):1649-56. doi: 10.1016/j.vaccine.2010.12.068. Epub 2011 Jan 4.
PMID: 21211579

Extracellular loops of lipid A 3-O-deacylase PagL are involved in recognition of aminoarabinose-based membrane modifications in Salmonella enterica serovar typhimurium
J Bacteriol. 2008 Aug;190(16):5597-606. doi: 10.1128/JB.00587-08. Epub 2008 Jun 20.
PMID: 18567660

Structural biology of membrane-intrinsic beta-barrel enzymes: sentinels of the bacterial outer membrane
Biochim Biophys Acta. 2008 Sep;1778(9):1881-96. doi: 10.1016/j.bbamem.2007.07.021. Epub 2007 Aug 11.
PMID: 17880914

Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL from Pseudomonas aeruginosa
Proc Natl Acad Sci U S A. 2006 May 2;103(18):7071-6. doi: 10.1073/pnas.0509392103. Epub 2006 Apr 21.
PMID: 16632613

Dissemination of lipid A deacylases (pagL) among gram-negative bacteria: identification of active-site histidine and serine residues
J Biol Chem. 2005 Mar 4;280(9):8248-59. doi: 10.1074/jbc.M414235200. Epub 2004 Dec 20.
PMID: 15611102

A PhoP/PhoQ-induced Lipase (PagL) that catalyzes 3-O-deacylation of lipid A precursors in membranes of Salmonella typhimurium
J Biol Chem. 2001 Mar 23;276(12):9083-92. doi: 10.1074/jbc.M010730200. Epub 2000 Dec 6.
PMID: 11108722

Proteins in this family with 3D-structure
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