3FID

LpxR from Salmonella typhimurium

Summary for 3FID

• Entry DOI: 10.2210/pdb3fid/pdb
• Descriptor: Putative outer membrane protein (LpxR), ZINC ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: lipopolysaccharide-modifying outer membrane enzyme, membrane protein
• Biological source: Salmonella typhimurium
• Total number of polymer chains: 2
• Total formula weight: 68825.38

Authors

Rutten, L.,Gros, P. (deposition date: 2008-12-11, release date: 2009-02-10, Last modification date: 2024-03-20)

Primary citation

Rutten, L.,Mannie, J.-P.B.A.,Stead, C.M.,Raetz, C.R.H.,Reynolds, C.M.,Bonvin, A.M.J.J.,Tommassen, J.P.,Egmond, M.R.,Trent, M.S.,Gros, P.
Active-site architecture and catalytic mechanism of the lipid A deacylase LpxR of Salmonella typhimurium
Proc.Natl.Acad.Sci.USA, 106:1960-1964, 2009

PubMed Abstract: The lipid A portion of lipopolysaccharide, the major component of the outer leaflet of the outer membrane of gram-negative bacteria, is toxic to humans. Modification of lipid A by enzymes often reduces its toxicity. The outer-membrane protein LpxR from Salmonella typhimurium is a lipid A-modifying enzyme. It removes the 3'-acyloxyacyl moiety of the lipid A portion of lipopolysaccharide in a Ca(2+)-dependent manner. Here, we present the crystal structure of S. typhimurium LpxR, crystallized in the presence of zinc ions. The structure, a 12-stranded beta-barrel, reveals that the active site is located between the barrel wall and an alpha-helix formed by an extracellular loop. Based on site-directed mutagenesis and modeling of a substrate on the active site, we propose a catalytic mechanism similar to that of phospholipase A2, in which a Ca(2+) forms the oxyanion hole and a histidine activates a water molecule (or a cascade of two water molecules) that subsequently attacks the carbonyl oxygen of the scissile bond.

PubMed: 19174515
DOI: 10.1073/pnas.0813064106

Experimental method

X-RAY DIFFRACTION (1.9 Å)