1p42
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /><applet load="1p42" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p42, resolution 2.00Å" /> '''Crystal structure of...)
Next diff →
Revision as of 21:20, 20 November 2007
|
Crystal structure of Aquifex aeolicus LpxC Deacetylase (Zinc-Inhibited Form)
Overview
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.
About this Structure
1P42 is a Single protein structure of sequence from Aquifex aeolicus with ZN and MYR as ligands. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Tue Nov 20 23:27:27 2007
