1p42 | pdb_00001p42

Crystal structure of Aquifex aeolicus LpxC Deacetylase (Zinc-Inhibited Form)

spinqualitylabelsall models 1p42, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1p42 is a 2 chain structure with sequence from "aquifex_aeolicus"_huber_and_stetter_2001 "aquifex aeolicus" huber and stetter 2001. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MYR, ZN Gene: LPXC OR ENVA OR AQ_1772 ("Aquifex aeolicus" Huber and Stetter 2001) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [LPXC_AQUAE] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The outer leaflet of the outer membrane of the Gram-negative bacterium serves as a permeability barrier and is composed of lipopolysaccharide, also known as endotoxin. The membrane anchor of lipopolysaccharide is lipid A, the biosynthesis of which is essential for cell viability. The first committed step in lipid A biosynthesis is catalyzed by UDP-(3-O-(R-3-hydroxymyristoyl))-N-acetylglucosamine deacetylase (LpxC), a zinc-dependent deacetylase. Here we report the crystal structure of LpxC from Aquifex aeolicus, which reveals a new alpha+beta fold reflecting primordial gene duplication and fusion, as well as a new zinc-binding motif. The catalytic zinc ion resides at the base of an active-site cleft and adjacent to a hydrophobic tunnel occupied by a fatty acid. This tunnel accounts for the specificity of LpxC toward substrates and inhibitors bearing appropriately positioned 3-O-fatty acid substituents. Notably, simple inhibitors designed to target interactions in the hydrophobic tunnel bind with micromolar affinity, thereby representing a step toward the structure-based design of a potent, broad-spectrum antibacterial drug. Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis.,Whittington DA, Rusche KM, Shin H, Fierke CA, Christianson DW Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8146-50. Epub 2003 Jun 20. PMID:12819349 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also UDP-3-O-acyl-N-acetylglucosamine deacetylase

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