1nhg

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[[Image:1nhg.gif|left|200px]]<br /><applet load="1nhg" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1nhg, resolution 2.43&Aring;" />
 
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'''CRYSTAL STRUCTURE ANALYSIS OF PLASMODIUM FALCIPARUM ENOYL-ACYL-CARRIER-PROTEIN REDUCTASE WITH TRICLOSAN'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE ANALYSIS OF PLASMODIUM FALCIPARUM ENOYL-ACYL-CARRIER-PROTEIN REDUCTASE WITH TRICLOSAN==
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The human malaria parasite Plasmodium falciparum synthesizes fatty acids using a type II pathway that is absent in humans. The final step in fatty acid elongation is catalyzed by enoyl acyl carrier protein reductase, a validated antimicrobial drug target. Here, we report the cloning and expression of the P. falciparum enoyl acyl carrier protein reductase gene, which encodes a 50-kDa protein (PfENR) predicted to target to the unique parasite apicoplast. Purified PfENR was crystallized, and its structure resolved as a binary complex with NADH, a ternary complex with triclosan and NAD(+), and as ternary complexes bound to the triclosan analogs 1 and 2 with NADH. Novel structural features were identified in the PfENR binding loop region that most closely resembled bacterial homologs; elsewhere the protein was similar to ENR from the plant Brassica napus (root mean square for Calphas, 0.30 A). Triclosan and its analogs 1 and 2 killed multidrug-resistant strains of intra-erythrocytic P. falciparum parasites at sub to low micromolar concentrations in vitro. These data define the structural basis of triclosan binding to PfENR and will facilitate structure-based optimization of PfENR inhibitors.
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<StructureSection load='1nhg' size='340' side='right'caption='[[1nhg]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1nhg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NHG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NHG FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.43&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=TCL:TRICLOSAN'>TCL</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nhg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nhg OCA], [https://pdbe.org/1nhg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nhg RCSB], [https://www.ebi.ac.uk/pdbsum/1nhg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nhg ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q9BH77_PLAFA Q9BH77_PLAFA]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nh/1nhg_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nhg ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1NHG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=TCL:'>TCL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NHG OCA].
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*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Structural elucidation of the specificity of the antibacterial agent triclosan for malarial enoyl acyl carrier protein reductase., Perozzo R, Kuo M, Sidhu AS, Valiyaveettil JT, Bittman R, Jacobs WR Jr, Fidock DA, Sacchettini JC, J Biol Chem. 2002 Apr 12;277(15):13106-14. Epub 2002 Jan 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11792710 11792710]
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[[Category: Large Structures]]
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[[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
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[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum]]
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[[Category: Protein complex]]
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[[Category: Bittman R]]
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[[Category: Bittman, R.]]
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[[Category: Fidock DA]]
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[[Category: Fidock, D A.]]
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[[Category: Jacobs Jr WR]]
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[[Category: Jr., W R.Jacobs.]]
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[[Category: Kuo M]]
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[[Category: Kuo, M.]]
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[[Category: Perozzo R]]
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[[Category: Perozzo, R.]]
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[[Category: Sacchettini JC]]
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[[Category: Sacchettini, J C.]]
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[[Category: Sidhu AS]]
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[[Category: Sidhu, A S.]]
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[[Category: Valiyaveettil JT]]
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[[Category: Valiyaveettil, J T.]]
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[[Category: NAD]]
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[[Category: TCL]]
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[[Category: nadh]]
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[[Category: rossmann fold]]
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[[Category: short chain dehydrogenase reductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:06:07 2008''
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Current revision

CRYSTAL STRUCTURE ANALYSIS OF PLASMODIUM FALCIPARUM ENOYL-ACYL-CARRIER-PROTEIN REDUCTASE WITH TRICLOSAN

PDB ID 1nhg

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