1vrw: Difference between revisions
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New page: left|200px<br /><applet load="1vrw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vrw, resolution 2.40Å" /> '''Crystal structure an... |
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== | ==Crystal structure analysis of plasmodium falciparum enoyl-acyl-carrier-protein reductase with nadh== | ||
The human malaria parasite Plasmodium falciparum synthesizes fatty acids | <StructureSection load='1vrw' size='340' side='right'caption='[[1vrw]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1vrw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1nhd 1nhd]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VRW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VRW FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1vrw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vrw OCA], [https://pdbe.org/1vrw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1vrw RCSB], [https://www.ebi.ac.uk/pdbsum/1vrw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1vrw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9BH77_PLAFA Q9BH77_PLAFA] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vr/1vrw_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=1vrw ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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:11792710<ref>PMID:11792710</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[ | <div class="pdbe-citations 1vrw" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
[[Category: Bittman R]] | |||
[[Category: Bittman | [[Category: Fidock DA]] | ||
[[Category: Fidock | [[Category: Jacobs Jr WR]] | ||
[[Category: Jr | [[Category: Kuo M]] | ||
[[Category: Kuo | [[Category: Perozzo R]] | ||
[[Category: Perozzo | [[Category: Sacchettini JC]] | ||
[[Category: Sacchettini | [[Category: Sidhu AS]] | ||
[[Category: Sidhu | [[Category: Valiyaveettil JT]] | ||
[[Category: Valiyaveettil | |||
Latest revision as of 03:05, 28 December 2023
Crystal structure analysis of plasmodium falciparum enoyl-acyl-carrier-protein reductase with nadhCrystal structure analysis of plasmodium falciparum enoyl-acyl-carrier-protein reductase with nadh
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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:11792710[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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