6OW0

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

6OW0 の概要

• エントリーDOI: 10.2210/pdb6ow0/pdb
• 分子名称: MtmW, DI(HYDROXYETHYL)ETHER, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• 機能のキーワード: natural product, biosynthesis, aureolic acid, reductase, oxidoreductase
• 由来する生物種: Streptomyces argillaceus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74451.82

構造登録者

Hou, C.,Yu, X.,Rohr, J.,Tsodikov, O.V. (登録日: 2019-05-08, 公開日: 2019-11-27, 最終更新日: 2023-10-11)

主引用文献

Wheeler, R.,Yu, X.,Hou, C.,Mitra, P.,Chen, J.M.,Herkules, F.,Ivanov, D.N.,Tsodikov, O.V.,Rohr, J.
Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis.
Angew.Chem.Int.Ed.Engl., 59:826-832, 2020

PubMed Abstract: 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 Mg 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 the ring-shaped β subunit of a vertebrate ion channel. We show that MtmW and MtmOIV 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.

PubMed: 31702856
DOI: 10.1002/anie.201910241

実験手法

X-RAY DIFFRACTION (2.67 Å)