4q9n: Difference between revisions
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The | ==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]] 1.79Å' 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]] 1.795Å</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> | |||
<div style="background-color:#fffaf0;"> | |||
== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<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]] | |||
Latest revision as of 17:30, 20 September 2023
Crystal structure of Chlamydia trachomatis enoyl-ACP reductase (FabI) in complex with NADH and AFN-1252
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