1pwq: Difference between revisions
New page: left|200px<br /><applet load="1pwq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pwq, resolution 3.52Å" /> '''Crystal structure of... |
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[[Image:1pwq.jpg|left|200px]]<br /><applet load="1pwq" size=" | [[Image:1pwq.jpg|left|200px]]<br /><applet load="1pwq" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1pwq, resolution 3.52Å" /> | caption="1pwq, resolution 3.52Å" /> | ||
'''Crystal structure of Anthrax Lethal Factor complexed with Thioacetyl-Tyr-Pro-Met-Amide, a metal-chelating peptidyl small molecule inhibitor'''<br /> | '''Crystal structure of Anthrax Lethal Factor complexed with Thioacetyl-Tyr-Pro-Met-Amide, a metal-chelating peptidyl small molecule inhibitor'''<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== | ||
1PWQ 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 SD2 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:// | 1PWQ 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=SD2:'>SD2</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=1PWQ 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: SD2]] | [[Category: SD2]] | ||
[[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 14:33:18 2008'' | ||
Revision as of 15:33, 21 February 2008
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Crystal structure of Anthrax Lethal Factor complexed with Thioacetyl-Tyr-Pro-Met-Amide, a metal-chelating peptidyl small molecule inhibitor
OverviewOverview
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 StructureAbout this Structure
1PWQ 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.
ReferenceReference
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
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