View source for 4q9n


==Crystal structure of Chlamydia trachomatis enoyl-ACP reductase (FabI) in complex with NADH and AFN-1252==
<StructureSection load='4q9n' size='340' side='right'caption='[[4q9n]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4q9n]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Chlamydia_trachomatis_F/11-96 Chlamydia trachomatis F/11-96]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q9N 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]] 1.795&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0WE:N-METHYL-N-[(3-METHYL-1-BENZOFURAN-2-YL)METHYL]-3-(7-OXO-5,6,7,8-TETRAHYDRO-1,8-NAPHTHYRIDIN-3-YL)PROPANAMIDE'>0WE</scene>, <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=4q9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9n OCA], [https://pdbe.org/4q9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q9n RCSB], [https://www.ebi.ac.uk/pdbsum/4q9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q9n ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The major phospholipid classes of the obligate intracellular bacterial parasite Chlamydia trachomatis are the same as its eukaryotic host except that they also contain chlamydia-made branched-chain fatty acids in the 2-position. Genomic analysis predicts that C. trachomatis is capable of type II fatty acid synthesis (FASII). AFN-1252 was deployed as a chemical tool to specifically inhibit the enoyl-acyl carrier protein reductase (FabI) of C. trachomatis to determine whether chlamydial FASII is essential for replication within the host. The C. trachomatis FabI (CtFabI) is a homotetramer and exhibited typical FabI kinetics, and its expression complemented an Escherichia coli fabI(Ts) strain. AFN-1252 inhibited CtFabI by binding to the FabI.NADH complex with an IC50 of 0.9 mum at saturating substrate concentration. The x-ray crystal structure of the CtFabI.NADH.AFN-1252 ternary complex revealed the specific interactions between the drug, protein, and cofactor within the substrate binding site. AFN-1252 treatment of C. trachomatis-infected HeLa cells at any point in the infectious cycle caused a decrease in infectious titers that correlated with a decrease in branched-chain fatty acid biosynthesis. AFN-1252 treatment at the time of infection prevented the first cell division of C. trachomatis, although the cell morphology suggested differentiation into a metabolically active reticulate body. These results demonstrate that FASII activity is essential for C. trachomatis proliferation within its eukaryotic host and validate CtFabI as a therapeutic target against C. trachomatis.

Type II Fatty Acid Synthesis Is Essential for the Replication of Chlamydia trachomatis.,Yao J, Abdelrahman YM, Robertson RM, Cox JV, Belland RJ, White SW, Rock CO J Biol Chem. 2014 Aug 8;289(32):22365-76. doi: 10.1074/jbc.M114.584185. Epub 2014, Jun 23. PMID:24958721<ref>PMID:24958721</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4q9n" 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: Chlamydia trachomatis F/11-96]]
[[Category: Large Structures]]
[[Category: Abdelrahman Y]]
[[Category: Belland RJ]]
[[Category: Cox JV]]
[[Category: Robertson RM]]
[[Category: Rock CO]]
[[Category: White SW]]
[[Category: Yao J]]