22as

The costructure of MitM and trans-1-hydroxy-7-methoxy-2-dimethylaminomitosene with SAH

spinqualitylabelsall models 22as, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 22as is a 2 chain structure with sequence from Streptomyces caespitosus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: A1E30, SAH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9X5Q9_STRLA Publication Abstract from PubMed S-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-O-MT for methylating the 6/5/5/3-fused aziridinomitosane (AMS) skeleton that is shared by many known mitomycin variables in C9 stereoselectivity and aziridine-N-methylation. Further, this MT can process AMS for C9a-O-methoxy elimination, aziridine hydrolysis/opening, and subsequent C1-O- and C2-N-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. A Methyltransferase Catalyzing Reactions More Than Methylation.,Wang S, Huang J, Xia M, Bi S, Wang J, Fang P, Liu W J Am Chem Soc. 2026 May 13;148(18):19061-19073. doi: 10.1021/jacs.6c02250. Epub , 2026 Apr 29. PMID:42057505 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA