6ow0

Crystal structure of mithramycin 3-side chain keto-reductase MtmW in complex with NAD+ and PEG

spinqualitylabelsall models 6ow0, resolution 2.67Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ow0 is a 2 chain structure with sequence from Streptomyces argillaceus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.67Å Ligands: GOL, NAP, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q194Q1_STRAA Publication Abstract from PubMed MtmOIV and MtmW catalyze the final two reactions in the mithramycin (MTM) biosynthetic pathway, the Baeyer-Villiger opening of the fourth ring of premithramycin B (PMB), creating the C3 pentyl side chain, strictly followed by reduction of the distal keto group on the new side chain. Unexpectedly this results in a C2 stereoisomer of mithramycin, iso-mithramycin (iso-MTM). Iso-MTM undergoes a non-enzymatic isomerization to MTM catalyzed by Mg2+ ions. Crystal structures of MtmW and its complexes with co-substrate NADPH and PEG, suggest a catalytic mechanism of MtmW. The structures also show that a tetrameric assembly of this enzyme strikingly resembles of the ring-shaped beta subunit of a vertebrate ion channel. We show that MtmW and MmOIV form a complex in the presence of PMB and NADPH, presumably to hand over the unstable MtmOIV product to MtmW, yielding iso-MTM, as a potential self-resistance mechanism against MTM toxicity. Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis.,Wheeler R, Yu X, Hou C, Mitra P, Chen JM, Herkules F, Ivanov DN, Tsodikov OV, Rohr J Angew Chem Int Ed Engl. 2019 Nov 8. doi: 10.1002/anie.201910241. PMID:31702856 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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