2ERV

Crystal structure of the outer membrane enzyme PagL

Summary for 2ERV

• Entry DOI: 10.2210/pdb2erv/pdb
• Descriptor: hypothetical protein Paer03002360, CALCIUM ION, PENTAETHYLENE GLYCOL MONODECYL ETHER, ... (4 entities in total)
• Functional Keywords: beta barrel, outer membrane, enzyme, hydrolase, lipopolysaccharide, membrane protein
• Biological source: Pseudomonas aeruginosa
• Cellular location: Cell outer membrane ; Multi-pass membrane protein : Q9HVD1
• Total number of polymer chains: 2
• Total formula weight: 36793.96

Authors

Rutten, L.,Geurtsen, J.,Lambert, W.,Smolenaers, J.J.,Bonvin, A.M.,van der Ley, P.,Egmond, M.R.,Gros, P.,Tommassen, J. (deposition date: 2005-10-25, release date: 2006-04-11, Last modification date: 2023-08-23)

Primary citation

Rutten, L.,Geurtsen, J.,Lambert, W.,Smolenaers, J.J.,Bonvin, A.M.,de Haan, A.,van der Ley, P.,Egmond, M.R.,Gros, P.,Tommassen, J.
Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL from Pseudomonas aeruginosa.
Proc.Natl.Acad.Sci.USA, 103:7071-7076, 2006

PubMed 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 hydrogen bond with the hydroxyl group of the 3-O-acyl chain, probably providing specificity of PagL toward lipid A.

PubMed: 16632613
DOI: 10.1073/pnas.0509392103

Experimental method

X-RAY DIFFRACTION (2 Å)