5nji | pdb_00005nji

Structure of the dehydratase domain of PpsC from Mycobacterium tuberculosis in complex with C12:1-CoA

spinqualitylabelsall models 5nji, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5nji is a 1 chain structure. This structure supersedes the now removed PDB entry 5cf7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 8Z2 Related: 4ooc, 5l84, 5i0k Activity: [acyl-carrier-protein_synthase_I Beta-ketoacyl-[acyl-carrier-protein] synthase I], with EC number 2.3.1.41 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PPSC_MYCBO] Involved in the elongation of either C22-24 fatty acids or p-hydroxyphenylalkanoic acids by the addition of malonyl-CoA and methylmalonyl-CoA extender units to yield phthiocerol and phenolphthiocerol derivatives, respectively. Publication Abstract from PubMed Dehydration reactions play a crucial role in the de novo biosynthesis of fatty acids and a wide range of pharmacologically active polyketide natural products with strong emphasis on human medicine. The type I polyketide synthase PpsC from Mycobacterium tuberculosis catalyzes key biosynthetic steps of lipid virulence factors phthiocerol dimycocerosates and phenolic glycolipids. Given the insolubility of the natural C28-C30 fatty acyl substrate of the PpsC dehydratase (DH) domain, we investigated its structure-function relationships in the presence of shorter surrogate substrates. Since most enzymes belonging to the (R)-specific enoyl hydratase/hydroxyacyl dehydratase family conduct the reverse hydration reaction in vitro, we have determined the X-ray structures of the PpsC DH domain, both unliganded (apo) and in complex with trans-but-2-enoyl-CoA or trans-dodec-2-enoyl-CoA derivatives. This study provides for the first time a snapshot of dehydratase-ligand interactions following a hydration reaction. Our structural analysis allowed us to identify residues essential for substrate binding and activity. The structural comparison of the two complexes also sheds light on the need for long acyl chains for this dehydratase to carry out its function, consistent with both its in vitro catalytic behavior and the physiological role of the PpsC enzyme. Insights into Substrate Modification by Dehydratases from Type I Polyketide Synthases.,Faille A, Gavalda S, Slama N, Lherbet C, Maveyraud L, Guillet V, Laval F, Quemard A, Mourey L, Pedelacq JD J Mol Biol. 2017 May 19;429(10):1554-1569. doi: 10.1016/j.jmb.2017.03.026. Epub, 2017 Apr 1. PMID:28377293 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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