5l3z

polyketide ketoreductase SimC7 - binary complex with NADP+

spinqualitylabelsall models 5l3z, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5l3z is a 1 chain structure with sequence from Streptomyces antibioticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: NAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G9VYV4_STRAT Publication Abstract from PubMed SimC7 is a polyketide ketoreductase involved in biosynthesis of the angucyclinone moiety of the gyrase inhibitor simocyclinone D8 (SD8). SimC7, which belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, catalyzes reduction of the C-7 carbonyl of the angucyclinone, and the resulting hydroxyl is essential for antibiotic activity. SimC7 shares little sequence similarity with characterized ketoreductases, suggesting it might have a distinct mechanism. To investigate this possibility, we determined the structures of SimC7 alone, with NADP(+), and with NADP(+) and the substrate 7-oxo-SD8. These structures show that SimC7 is distinct from previously characterized polyketide ketoreductases, lacking the conserved catalytic triad, including the active-site tyrosine that acts as central acid-base catalyst in canonical SDR proteins. Taken together with functional analyses of active-site mutants, our data suggest that SimC7 catalyzes a substrate-assisted, two-step reaction for reduction of the C-7 carbonyl group involving intramolecular transfer of a substrate-derived proton to generate a phenolate intermediate. Substrate-Assisted Catalysis in Polyketide Reduction Proceeds via a Phenolate Intermediate.,Schafer M, Stevenson CE, Wilkinson B, Lawson DM, Buttner MJ Cell Chem Biol. 2016 Sep 22;23(9):1091-7. doi: 10.1016/j.chembiol.2016.07.018., Epub 2016 Sep 8. PMID:27617849 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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