View source for 3am5


==K316A mutant of Enoyl-ACP Reductase from Plasmodium falciparum (PfENR) in complex with triclosan==
<StructureSection load='3am5' size='340' side='right'caption='[[3am5]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3am5]] is a 2 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=3AM5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AM5 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]] 2.05&#8491;</td></tr>
<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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3am5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3am5 OCA], [https://pdbe.org/3am5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3am5 RCSB], [https://www.ebi.ac.uk/pdbsum/3am5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3am5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9BJJ9_PLAFA Q9BJJ9_PLAFA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Enoyl acyl carrier protein reductase (ENR), which catalyzes the final and rate limiting step of fatty acid elongation, has been validated as a potential drug target. Triclosan is known to be an effective inhibitor for this enzyme. We mutated the substrate binding site residue Ala372 of the ENR of Plasmodium falciparum (PfENR) to Methionine and Valine which increased the affinity of the enzyme towards triclosan to almost double, close to that of Escherichia coli ENR (EcENR) which has a Methionine at the structurally similar position of Ala372 of PfENR. Kinetic studies of the mutants of PfENR and the crystal structure analysis of the A372M mutant revealed that a more hydrophobic environment enhances the affinity of the enzyme for the inhibitor. A triclosan derivative showed a threefold increase in the affinity towards the mutants compared to the wild type, due to additional interactions with the A372M mutant as revealed by the crystal structure. The enzyme has a conserved salt bridge which stabilizes the substrate binding loop and appears to be important for the active conformation of the enzyme. We generated a second set of mutants to check this hypothesis. These mutants showed loss of function, except in one case, where the crystal structure showed that the substrate binding loop is stabilized by a water bridge network.

Effect of substrate binding loop mutations on the structure, kinetics, and inhibition of enoyl acyl carrier protein reductase from plasmodium falciparum.,Maity K, Banerjee T, Prabakaran N, Surolia N, Surolia A, Suguna K IUBMB Life. 2011 Jan;63(1):30-41. doi: 10.1002/iub.412. Epub 2011 Jan 13. PMID:21280175<ref>PMID:21280175</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3am5" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Banerjee T]]
[[Category: Maity K]]
[[Category: Narayanappa P]]
[[Category: Suguna K]]
[[Category: Surolia A]]
[[Category: Surolia N]]