| Autor: |
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.M., Egmond, M.R., Trent, M.S., Gros, P. |
| Přispěvatelé: |
Crystal and Structural Chemistry, Membrane Enzymology, Molecular Microbiology, NMR Spectroscopy, Dep Scheikunde, Dep Biologie, Sub Molecular Microbiology, Sub Membrane Enzymology begr. 01-06-12, Sub Algemeen Scheikunde, Sub Crystal and Structural Chemistry |
| Rok vydání: |
2009 |
| Popis: |
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 Ca2+-dependent manner. Here, we present the crystal structure of S. typhimurium LpxR, crystallized in the presence of zinc ions. The structure, a 12-stranded β-barrel, reveals that the active site is located between the barrel wall and an α-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 Ca2+ 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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