5nci | pdb_00005nci

GriE in complex with cobalt, alpha-ketoglutarate and l-leucine

spinqualitylabelsall models 5nci, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5nci is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AKG, CO, LEU, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Griselimycins (GMs) are depsidecapeptides with superb anti-tuberculosis activity. They contain up to three (2S,4R)-4-methyl-prolines (4-MePro), of which one blocks oxidative degradation and increases metabolic stability in animal models. The natural congener with this substitution is only a minor component in fermentation cultures. We showed that this product can be significantly increased by feeding the reaction with 4-MePro and we investigated the molecular basis of 4-MePro biosynthesis and incorporation. We identified the GM biosynthetic gene cluster as encoding a nonribosomal peptide synthetase and a sub-operon for 4-MePro formation. Using heterologous expression, gene inactivation, and in vitro experiments, we showed that 4-MePro is generated by leucine hydroxylation, oxidation to an aldehyde, and ring closure with subsequent reduction. The crystal structures of the leucine hydroxylase GriE have been determined in complex with substrates and products, providing insight into the stereospecificity of the reaction. Biosynthesis of methyl-proline containing griselimycins, natural products with anti-tuberculosis activity.,Lukat P, Katsuyama Y, Wenzel S, Binz T, Konig C, Blankenfeldt W, Bronstrup M, Muller R Chem Sci. 2017 Nov 1;8(11):7521-7527. doi: 10.1039/c7sc02622f. Epub 2017 Aug 3. PMID:29163906 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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