1zxv
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1zxv |SIZE=350|CAPTION= <scene name='initialview01'>1zxv</scene>, resolution 2.67Å | |PDB= 1zxv |SIZE=350|CAPTION= <scene name='initialview01'>1zxv</scene>, resolution 2.67Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=MFM:(E)-3-(5((5-(4-CHLOROPHENYL)FURAN-2-YL)METHYLENE)-4-OXO-2-THIOXOTHIAZOLIDIN-3-YL)PROPANOIC+ACID'>MFM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Anthrax_lethal_factor_endopeptidase Anthrax lethal factor endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.83 3.4.24.83] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Anthrax_lethal_factor_endopeptidase Anthrax lethal factor endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.83 3.4.24.83] </span> |
|GENE= lef ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 Bacillus anthracis]) | |GENE= lef ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 Bacillus anthracis]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zxv OCA], [http://www.ebi.ac.uk/pdbsum/1zxv PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zxv RCSB]</span> | ||
}} | }} | ||
| Line 25: | Line 28: | ||
[[Category: Liddington, R C.]] | [[Category: Liddington, R C.]] | ||
[[Category: Wong, T Y.]] | [[Category: Wong, T Y.]] | ||
| - | [[Category: MFM]] | ||
| - | [[Category: ZN]] | ||
[[Category: anthrax toxin lethal factor]] | [[Category: anthrax toxin lethal factor]] | ||
[[Category: protein and small molecule inhibitor complex]] | [[Category: protein and small molecule inhibitor complex]] | ||
[[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 Mon Mar 31 01:43:02 2008'' |
Revision as of 22:43, 30 March 2008
| |||||||
| , resolution 2.67Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | lef (Bacillus anthracis) | ||||||
| Activity: | Anthrax lethal factor endopeptidase, with EC number 3.4.24.83 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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 Mon Mar 31 01:43:02 2008
