7pcg

BurG (holo) in complex with cyclopropane-1,1-dicarboxylate (7): Biosynthesis of cyclopropanol rings in bacterial toxins

spinqualitylabelsall models 7pcg, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7pcg is a 2 chain structure with sequence from Burkholderia thailandensis E264. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: 9TY, GOL, MG, NAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q2T3G7_BURTA Publication Abstract from PubMed Bacteria of the Burkholderia pseudomallei (BP) group pose a global health threat, causing the infectious diseases melioidosis, a common cause of pneumonia and sepsis, and glanders, a contagious zoonosis. A trait of BP bacteria is a conserved gene cluster coding for the biosynthesis of polyketides (malleicyprols) with a reactive cyclopropanol unit that is critical for virulence. Enzymes building this warhead represent ideal targets for antivirulence strategies but the biochemical basis of cyclopropanol formation is unknown. Here we describe the formation of the malleicyprol warhead. We show that BurG, an unusual NAD(+)-dependent member of the ketol-acid reductoisomerase family, constructs the strained cyclopropanol ring. Biochemical assays and a suite of eight crystal structures of native and mutated BurG with bound analogues and inhibitors provide snapshots of each step of the complex reaction mechanism, involving a concealed oxidoreduction and a C-S bond cleavage. Our findings illustrate a remarkable case of neofunctionalisation, where a biocatalyst from central metabolism has been evolutionarily repurposed for warhead production in pathogens. Pathogenic bacteria remodel central metabolic enzyme to build a cyclopropanol warhead.,Trottmann F, Ishida K, Ishida-Ito M, Kries H, Groll M, Hertweck C Nat Chem. 2022 Aug;14(8):884-890. doi: 10.1038/s41557-022-01005-z. Epub 2022 Jul , 29. PMID:35906404 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ketol-acid reductoisomerase 3D structures

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