2jt2 | pdb_00002jt2

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Solution Structure of the Aquifex aeolicus LpxC- CHIR-090 complex

spinqualitylabelsall models 2jt2, 25 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2jt2 is a 1 chain structure with sequence from "aquifex_aeolicus"_huber_and_stetter_2001 "aquifex aeolicus" huber and stetter 2001. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: C90, ZN Gene: lpxC, envA ("Aquifex aeolicus" Huber and Stetter 2001) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Warning: this is a large structure, and loading might take a long time or not happen at all. 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 UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC is an essential enzyme of lipid A biosynthesis in Gram-negative bacteria and a promising antibiotic target. CHIR-090, the most potent LpxC inhibitor discovered to date, displays two-step time-dependent inhibition and kills a wide range of Gram-negative pathogens as effectively as ciprofloxacin or tobramycin. In this study, we report the solution structure of the LpxC-CHIR-090 complex. CHIR-090 exploits conserved features of LpxC that are critical for catalysis, including the hydrophobic passage and essential active-site residues. CHIR-090 is adjacent to, but does not occupy, the UDP-binding pocket of LpxC, suggesting that a fragment-based approach may facilitate further optimization of LpxC inhibitors. Additionally, we identified key residues in the Insert II hydrophobic passage that modulate time-dependent inhibition and CHIR-090 resistance. CHIR-090 shares a similar, although previously unrecognized, chemical scaffold with other small-molecule antibiotics such as L-161,240 targeting LpxC, and provides a template for understanding the binding mode of these inhibitors. Consistent with this model, we provide evidence that L-161,240 also occupies the hydrophobic passage. Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: Time-dependent inhibition and specificity in ligand binding.,Barb AW, Jiang L, Raetz CR, Zhou P Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18433-8. Epub 2007 Nov 19. PMID:18025458 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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