1pwp: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: left|200px<br /><applet load="1pwp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pwp, resolution 2.90Å" /> '''Crystal Structure of... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1pwp.gif|left|200px]]<br /><applet load="1pwp" size=" | [[Image:1pwp.gif|left|200px]]<br /><applet load="1pwp" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1pwp, resolution 2.90Å" /> | caption="1pwp, resolution 2.90Å" /> | ||
'''Crystal Structure of the Anthrax Lethal Factor complexed with Small Molecule Inhibitor NSC 12155'''<br /> | '''Crystal Structure of the Anthrax Lethal Factor complexed with Small Molecule Inhibitor NSC 12155'''<br /> | ||
==Overview== | ==Overview== | ||
The virulent spore-forming bacterium Bacillus anthracis secretes anthrax | 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. | ||
==About this Structure== | ==About this Structure== | ||
1PWP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] with ZN and NSC as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 1PWP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=NSC:'>NSC</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PWP OCA]. | ||
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Bacillus anthracis]] | [[Category: Bacillus anthracis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Liddington, R | [[Category: Liddington, R C.]] | ||
[[Category: Schwarzenbacher, R.]] | [[Category: Schwarzenbacher, R.]] | ||
[[Category: Wong, T | [[Category: Wong, T Y.]] | ||
[[Category: NSC]] | [[Category: NSC]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
| Line 23: | Line 23: | ||
[[Category: small molecule inhibitor]] | [[Category: small molecule inhibitor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:33:18 2008'' | ||
