1zxb
From Proteopedia
(New page: 200px<br /><applet load="1zxb" size="350" color="white" frame="true" align="right" spinBox="true" caption="1zxb, resolution 2.68Å" /> '''Synthesis, Biologica...) |
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==Overview== | ==Overview== | ||
| - | A structure-based approach has been taken to develop 4'-substituted | + | A structure-based approach has been taken to develop 4'-substituted analogs of triclosan that target the key malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Many of these compounds exhibit nanomolar potency against purified PfENR enzyme and modest (2-10microM) potency against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite. X-ray crystal structures of nitro 29, aniline 30, methylamide 37, and urea 46 demonstrate the presence of hydrogen-bonding interactions with residues in the active site and point to future rounds of optimization to improve compound potency against purified enzyme and intracellular parasites. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Anderson, J | + | [[Category: Anderson, J W.]] |
| - | [[Category: Fidock, D | + | [[Category: Fidock, D A.]] |
| - | [[Category: Freundlich, J | + | [[Category: Freundlich, J S.]] |
| - | [[Category: Jacobus, D | + | [[Category: Jacobus, D P.]] |
| - | [[Category: Jr., W | + | [[Category: Jr., W R.Jacobs.]] |
[[Category: Kuo, M.]] | [[Category: Kuo, M.]] | ||
[[Category: Lucumi, E.]] | [[Category: Lucumi, E.]] | ||
| - | [[Category: Sacchettini, J | + | [[Category: Sacchettini, J C.]] |
[[Category: Sarantakis, D.]] | [[Category: Sarantakis, D.]] | ||
| - | [[Category: Schiehser, G | + | [[Category: Schiehser, G A.]] |
| - | [[Category: Shieh, H | + | [[Category: Shieh, H M.]] |
[[Category: Yu, M.]] | [[Category: Yu, M.]] | ||
[[Category: NAD]] | [[Category: NAD]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''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 16:19:59 2008'' |
Revision as of 14:20, 21 February 2008
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Synthesis, Biological Activity, and X-Ray Crystal Structural Analysis of Diaryl Ether Inhibitors of Malarial Enoyl ACP Reductase. Part 1:4'-Substituted Triclosan Derivatives
Overview
A structure-based approach has been taken to develop 4'-substituted analogs of triclosan that target the key malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Many of these compounds exhibit nanomolar potency against purified PfENR enzyme and modest (2-10microM) potency against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite. X-ray crystal structures of nitro 29, aniline 30, methylamide 37, and urea 46 demonstrate the presence of hydrogen-bonding interactions with residues in the active site and point to future rounds of optimization to improve compound potency against purified enzyme and intracellular parasites.
About this Structure
1ZXB is a Single protein structure of sequence from Plasmodium falciparum with and as ligands. Active as [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9 Full crystallographic information is available from OCA.
Reference
Synthesis, biological activity, and X-ray crystal structural analysis of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 1: 4'-substituted triclosan derivatives., Freundlich JS, Anderson JW, Sarantakis D, Shieh HM, Yu M, Valderramos JC, Lucumi E, Kuo M, Jacobs WR Jr, Fidock DA, Schiehser GA, Jacobus DP, Sacchettini JC, Bioorg Med Chem Lett. 2005 Dec 1;15(23):5247-52. Epub 2005 Sep 29. PMID:16198563 [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
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