1pwu
From Proteopedia
(New page: 200px<br /><applet load="1pwu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pwu, resolution 2.70Å" /> '''Crystal Structure of...) |
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| - | [[Image:1pwu.jpg|left|200px]]<br /><applet load="1pwu" size=" | + | [[Image:1pwu.jpg|left|200px]]<br /><applet load="1pwu" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1pwu, resolution 2.70Å" /> | caption="1pwu, resolution 2.70Å" /> | ||
'''Crystal Structure of Anthrax Lethal Factor complexed with (3-(N-hydroxycarboxamido)-2-isobutylpropanoyl-Trp-methylamide), a known small molecule inhibitor of matrix metalloproteases.'''<br /> | '''Crystal Structure of Anthrax Lethal Factor complexed with (3-(N-hydroxycarboxamido)-2-isobutylpropanoyl-Trp-methylamide), a known small molecule inhibitor of matrix metalloproteases.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Recent events have created an urgent need for new therapeutic strategies | + | Recent events have created an urgent need for new therapeutic strategies to treat anthrax. We have applied a mixture-based peptide library approach to rapidly determine the optimal peptide substrate for the anthrax lethal factor (LF), a metalloproteinase with an important role in the pathogenesis of the disease. Using this approach we have identified peptide analogs that inhibit the enzyme in vitro and that protect cultured macrophages from LF-mediated cytolysis. The crystal structures of LF bound to an optimized peptide substrate and to peptide-based inhibitors provide a rationale for the observed selectivity and may be exploited in the design of future generations of LF inhibitors. |
==About this Structure== | ==About this Structure== | ||
| - | 1PWU 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 GM6 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1PWU 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=GM6:'>GM6</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PWU OCA]. |
==Reference== | ==Reference== | ||
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[[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: GM6]] | [[Category: GM6]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: small molecule peptidic inhibitor]] | [[Category: small molecule peptidic inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:33:23 2008'' |
Revision as of 12:33, 21 February 2008
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Crystal Structure of Anthrax Lethal Factor complexed with (3-(N-hydroxycarboxamido)-2-isobutylpropanoyl-Trp-methylamide), a known small molecule inhibitor of matrix metalloproteases.
Overview
Recent events have created an urgent need for new therapeutic strategies to treat anthrax. We have applied a mixture-based peptide library approach to rapidly determine the optimal peptide substrate for the anthrax lethal factor (LF), a metalloproteinase with an important role in the pathogenesis of the disease. Using this approach we have identified peptide analogs that inhibit the enzyme in vitro and that protect cultured macrophages from LF-mediated cytolysis. The crystal structures of LF bound to an optimized peptide substrate and to peptide-based inhibitors provide a rationale for the observed selectivity and may be exploited in the design of future generations of LF inhibitors.
About this Structure
1PWU is a Single protein structure of sequence from Bacillus anthracis with and as ligands. Full crystallographic information is available from OCA.
Reference
The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor., Turk BE, Wong TY, Schwarzenbacher R, Jarrell ET, Leppla SH, Collier RJ, Liddington RC, Cantley LC, Nat Struct Mol Biol. 2004 Jan;11(1):60-6. Epub 2003 Dec 29. PMID:14718924
Page seeded by OCA on Thu Feb 21 14:33:23 2008
