4q9n | pdb_00004q9n

Crystal structure of Chlamydia trachomatis enoyl-ACP reductase (FabI) in complex with NADH and AFN-1252

spinqualitylabelsall models 4q9n, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4q9n is a 8 chain structure with sequence from Chlamydia trachomatis F/11-96. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.795Å Ligands: 0WE, NAI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Enoyl-Acyl-Carrier Protein Reductase 3D structures

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