1pwp | pdb_00001pwp

Crystal Structure of the Anthrax Lethal Factor complexed with Small Molecule Inhibitor NSC 12155

spinqualitylabelsall models 1pwp, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1pwp is a 2 chain structure with sequence from Bacillus anthracis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NSC, ZN Related: 1pwq Gene: LEF (Bacillus anthracis) Activity: Anthrax lethal factor endopeptidase, with EC number 3.4.24.83 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The virulent spore-forming bacterium Bacillus anthracis secretes anthrax toxin composed of protective antigen (PA), lethal factor (LF) and edema factor (EF). LF is a Zn-dependent metalloprotease that inactivates key signaling molecules, such as mitogen-activated protein kinase kinases (MAPKK), to ultimately cause cell death. We report here the identification of small molecule (nonpeptidic) inhibitors of LF. Using a two-stage screening assay, we determined the LF inhibitory properties of 19 compounds. Here, we describe six inhibitors on the basis of a pharmacophoric relationship determined using X-ray crystallographic data, molecular docking studies and three-dimensional (3D) database mining from the US National Cancer Institute (NCI) chemical repository. Three of these compounds have K(i) values in the 0.5-5 microM range and show competitive inhibition. These molecular scaffolds may be used to develop therapeutically viable inhibitors of LF. Identification of small molecule inhibitors of anthrax lethal factor.,Panchal RG, Hermone AR, Nguyen TL, Wong TY, Schwarzenbacher R, Schmidt J, Lane D, McGrath C, Turk BE, Burnett J, Aman MJ, Little S, Sausville EA, Zaharevitz DW, Cantley LC, Liddington RC, Gussio R, Bavari S Nat Struct Mol Biol. 2004 Jan;11(1):67-72. Epub 2003 Dec 29. PMID:14718925 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Anthrax Lethal Factor

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