5l84 | pdb_00005l84

Structure of the H959F variant of the PpsC dehydratase domain from Mycobacterium tuberculosis

spinqualitylabelsall models 5l84, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5l84 is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PPSC_MYCTU Involved in the elongation of either C22-24 fatty acids by the addition of malonyl-CoA and methylmalonyl-CoA extender units to yield phthiocerol derivatives. 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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