2nq8: Difference between revisions
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|PDB= 2nq8 |SIZE=350|CAPTION= <scene name='initialview01'>2nq8</scene>, resolution 2.50Å | |PDB= 2nq8 |SIZE=350|CAPTION= <scene name='initialview01'>2nq8</scene>, resolution 2.50Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=ZID:ISONICOTINIC-ACETYL-NICOTINAMIDE-ADENINE DINUCLEOTIDE'>ZID</scene> | |LIGAND= <scene name='pdbligand=ZID:ISONICOTINIC-ACETYL-NICOTINAMIDE-ADENINE+DINUCLEOTIDE'>ZID</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= FabI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 Plasmodium falciparum]) | |GENE= FabI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 Plasmodium falciparum]) | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2nq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nq8 OCA], [http://www.ebi.ac.uk/pdbsum/2nq8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2nq8 RCSB]</span> | |||
}} | }} | ||
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[[Category: Valderramos, J C.]] | [[Category: Valderramos, J C.]] | ||
[[Category: Yu, M.]] | [[Category: Yu, M.]] | ||
[[Category: | [[Category: inh]] | ||
[[Category: pfenr | [[Category: malaria]] | ||
[[Category: pfenr]] | |||
''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 04:06:46 2008'' | ||
Revision as of 04:06, 31 March 2008
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| , resolution 2.50Å | |||||||
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| Ligands: | |||||||
| Gene: | FabI (Plasmodium falciparum) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Malarial enoyl acyl ACP reductase bound with INH-NAD adduct
OverviewOverview
The x-ray crystal structures of five triclosan analogs, in addition to that of the isoniazid-NAD adduct, are described in relation to their integral role in the design of potent inhibitors of the malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Many of the novel 5-substituted analogs exhibit low micromolar potency against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite and inhibit purified PfENR enzyme with IC50 values of <200 nM. This study has significantly expanded the knowledge base with regard to the structure-activity relationship of triclosan while affording gains against cultured parasites and purified PfENR enzyme. In contrast to a recent report in the literature, these results demonstrate the ability to improve the in vitro potency of triclosan significantly by replacing the suboptimal 5-chloro group with larger hydrophobic moieties. The biological and x-ray crystallographic data thus demonstrate the flexibility of the active site and point to future rounds of optimization to improve compound potency against purified enzyme and intracellular Plasmodium parasites.
About this StructureAbout this Structure
2NQ8 is a Protein complex structure of sequences from Plasmodium falciparum. Full crystallographic information is available from OCA.
ReferenceReference
X-ray structural analysis of Plasmodium falciparum enoyl acyl carrier protein reductase as a pathway toward the optimization of triclosan antimalarial efficacy., Freundlich JS, Wang F, Tsai HC, Kuo M, Shieh HM, Anderson JW, Nkrumah LJ, Valderramos JC, Yu M, Kumar TR, Valderramos SG, Jacobs WR Jr, Schiehser GA, Jacobus DP, Fidock DA, Sacchettini JC, J Biol Chem. 2007 Aug 31;282(35):25436-44. Epub 2007 Jun 13. PMID:17567585
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