1xxe

RDC refined solution structure of the AaLpxC/TU-514 complex

spinqualitylabelsall models 1xxe Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1xxe is a 1 chain structure with sequence from Aquifex aeolicus. This structure supersedes the now removed PDB entry 1nzt. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: TUX, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 Lipopolysaccharide, the major constituent of the outer monolayer of the outer membrane of Gram-negative bacteria, is anchored into the membrane through the hydrophobic moiety lipid A, a hexaacylated disaccharide. The zinc-dependent metalloamidase UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) catalyzes the second and committed step in the biosynthesis of lipid A. LpxC shows no homology to mammalian metalloamidases and is essential for cell viability, making it an important target for the development of novel antibacterial compounds. Recent NMR and X-ray studies of the LpxC from Aquifex aeolicus have provided the first structural information about this family of proteins. Insight into the catalytic mechanism and the design of effective inhibitors could be facilitated by more detailed structural and biochemical studies that define substrate-protein interactions and the roles of specific residues in the active site. Here, we report the synthesis of the (13)C-labeled substrate-analogue inhibitor TU-514, and the subsequent refinement of the solution structure of the A. aeolicus LpxC-TU-514 complex using residual dipolar couplings. We also reevaluate the catalytic role of an active site histidine, H253, on the basis of both its pK(a) as determined by NMR titration and pH-dependent kinetic analyses. These results provide a structural basis for the design of more potent LpxC inhibitors than those that are currently available. Refined solution structure of the LpxC-TU-514 complex and pKa analysis of an active site histidine: insights into the mechanism and inhibitor design.,Coggins BE, McClerren AL, Jiang L, Li X, Rudolph J, Hindsgaul O, Raetz CR, Zhou P Biochemistry. 2005 Feb 1;44(4):1114-26. PMID:15667205 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also UDP-3-O-acyl-N-acetylglucosamine deacetylase UDP-3-O-acyl-N-acetylglucosamine deacetylase 3D structures

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