22AE

The costructure of MitM and mitomycin F with SAH

これはPDB形式変換不可エントリーです。

22AE の概要

• エントリーDOI: 10.2210/pdb22ae/pdb
• 分子名称: MitM, S-ADENOSYL-L-HOMOCYSTEINE, [(4S,6S,7R,8S)-7,11-dimethoxy-5,12-dimethyl-10,13-dioxo-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-dien-8-yl]methyl carbamate, ... (4 entities in total)
• 機能のキーワード: sam-dependent methyltransferase, transferase
• 由来する生物種: Streptomyces caespitosus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64960.37

構造登録者

Xia, M.,Wang, S.,Fang, P.,Liu, W. (登録日: 2026-01-05, 公開日: 2026-05-20, 最終更新日: 2026-05-27)

主引用文献

Wang, S.,Huang, J.,Xia, M.,Bi, S.,Wang, J.,Fang, P.,Liu, W.
A Methyltransferase Catalyzing Reactions More Than Methylation.
J.Am.Chem.Soc., 148:19061-19073, 2026

PubMed Abstract: -Adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) play important roles in many biological processes by catalyzing a methylation reaction. Proteins with a similar MT-fold to enable catalytic abilities rather than methylation were evidenced, but revealing these abilities appears to be a challenge to bioinformatics analysis unless experimental efforts are involved. Based on comprehensive investigations into MitM in the biosynthesis of mitomycins, the clinically important antitumor antibiotics, we report here that this MT catalyzes reactions more than methylation. MitM primarily acts as a C9a--MT for methylating the 6/5/5/3-fused ziridinoitoane (AMS) skeleton that is shared by many known mitomycin variables in C9 stereoselectivity and aziridine--methylation. Further, this MT can process AMS for C9a--methoxy elimination, aziridine hydrolysis/opening, and subsequent C1-- and C2--methylations. Gene inactivation, biochemical characterization, substrate/product cocrystallization, and site-specific mutagenesis rationalized the mechanisms by which the MT-fold of MitM is repurposed to deliver such an extraordinary capability, facilitating the observation of a few new antitumor mitomycins that were not recognized previously in the producing strain. This study attracts attention to uncharacterized MT-fold proteins, which have millions of sequences in databases but remain to be appreciated in catalytic function.

PubMed: 42057505
DOI: 10.1021/jacs.6c02250

実験手法

X-RAY DIFFRACTION (2.99 Å)