1zxv
From Proteopedia
(New page: 200px<br /><applet load="1zxv" size="350" color="white" frame="true" align="right" spinBox="true" caption="1zxv, resolution 2.67Å" /> '''X-Ray Crystal Struct...) |
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==Overview== | ==Overview== | ||
| - | Inhalation anthrax is a deadly disease for which there is currently no | + | Inhalation anthrax is a deadly disease for which there is currently no effective treatment. Bacillus anthracis lethal factor (LF) metalloproteinase is an integral component of the tripartite anthrax lethal toxin that is essential for the onset and progression of anthrax. We report here on a fragment-based approach that allowed us to develop inhibitors of LF. The small-molecule inhibitors we have designed, synthesized, and tested are highly potent and selective against LF in both in vitro tests and cell-based assays. These inhibitors do not affect the prototype human metalloproteinases that are structurally similar to LF. Initial in vivo evaluation of postexposure efficacy of our inhibitors combined with antibiotic ciprofloxacin against B. anthracis resulted in significant protection. Our data strongly indicate that the scaffold of inhibitors we have identified is the foundation for the development of novel, safe, and effective emergency therapy of postexposure inhalation anthrax. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Bacillus anthracis]] | [[Category: Bacillus anthracis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Liddington, R | + | [[Category: Liddington, R C.]] |
| - | [[Category: Wong, T | + | [[Category: Wong, T Y.]] |
[[Category: MFM]] | [[Category: MFM]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: zinc metalloproteinase]] | [[Category: zinc metalloproteinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:20:07 2008'' |
Revision as of 14:20, 21 February 2008
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X-Ray Crystal Structure of the Anthrax Lethal Factor Bound to a Small Molecule Inhibitor, BI-MFM3, 3-{5-[5-(4-Chloro-phenyl)-furan-2-ylmethylene]-4-oxo-2-thioxo-thiazolidin-3-yl}-propionic acid.
Overview
Inhalation anthrax is a deadly disease for which there is currently no effective treatment. Bacillus anthracis lethal factor (LF) metalloproteinase is an integral component of the tripartite anthrax lethal toxin that is essential for the onset and progression of anthrax. We report here on a fragment-based approach that allowed us to develop inhibitors of LF. The small-molecule inhibitors we have designed, synthesized, and tested are highly potent and selective against LF in both in vitro tests and cell-based assays. These inhibitors do not affect the prototype human metalloproteinases that are structurally similar to LF. Initial in vivo evaluation of postexposure efficacy of our inhibitors combined with antibiotic ciprofloxacin against B. anthracis resulted in significant protection. Our data strongly indicate that the scaffold of inhibitors we have identified is the foundation for the development of novel, safe, and effective emergency therapy of postexposure inhalation anthrax.
About this Structure
1ZXV is a Single protein structure of sequence from Bacillus anthracis with and as ligands. Active as Anthrax lethal factor endopeptidase, with EC number 3.4.24.83 Full crystallographic information is available from OCA.
Reference
Efficient synthetic inhibitors of anthrax lethal factor., Forino M, Johnson S, Wong TY, Rozanov DV, Savinov AY, Li W, Fattorusso R, Becattini B, Orry AJ, Jung D, Abagyan RA, Smith JW, Alibek K, Liddington RC, Strongin AY, Pellecchia M, Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9499-504. Epub 2005 Jun 27. PMID:15983377
Page seeded by OCA on Thu Feb 21 16:20:07 2008
