Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wheeler R, Yu X, Hou C, Mitra P, Chen JM, Herkules F, Ivanov DN, Tsodikov OV, Rohr J. Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis. Angew Chem Int Ed Engl. 2019 Nov 8. doi: 10.1002/anie.201910241. PMID:31702856 doi:http://dx.doi.org/10.1002/anie.201910241