4lcf

Crystal structure of the Pseudomonas aeruginosa LPXC/LPC-014 complexCrystal structure of the Pseudomonas aeruginosa LPXC/LPC-014 complex

Structural highlights 4lcf is a 1 chain structure with sequence from Pseae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , Related: 4lcg, 4lch Gene: envA, lpxC, PA4406 (PSEAE) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [LPXC_PSEAE] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell. Publication Abstract from PubMed The zinc-dependent deacetylase LpxC catalyzes the committed step of lipid A biosynthesis in Gram-negative bacteria and is a validated target for development of novel antibiotics to combat multidrug-resistant Gram-negative infections. Many potent LpxC inhibitors contain an essential threonyl-hydroxamate head group for high-affinity interaction with LpxC. We report the synthesis, antibiotic activity, and structural and enzymatic characterization of novel LpxC inhibitors containing an additional aryl-group in the threonyl-hydroxamate moiety, which expands the inhibitor-binding surface in LpxC. These compounds display enhanced potency against LpxC in enzymatic assays and superior antibiotic activity against F. novicida in cell culture. Comparison of the antibiotic activities of these compounds against a leaky E. coli strain and the wild-type strain reveals the contribution of the formidable outer membrane permeability barrier that reduces the compound efficacy in cell culture and emphasizes the importance of maintaining a balanced hydrophobicity and hydrophilicity profile in developing effective LpxC-targeting antibiotics. Synthesis, structure and antibiotic activity of aryl-substituted LpxC inhibitors.,Liang X, Lee CJ, Zhao J, Toone EJ, Zhou P J Med Chem. 2013 Aug 5. PMID:23914798 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4lcf, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image