22AS
The costructure of MitM and trans-1-hydroxy-7-methoxy-2-dimethylaminomitosene with SAH
This is a non-PDB format compatible entry.
Summary for 22AS
| Entry DOI | 10.2210/pdb22as/pdb |
| Descriptor | MitM, S-ADENOSYL-L-HOMOCYSTEINE, [(2~{S},3~{R})-2-(dimethylamino)-6-methoxy-7-methyl-3-oxidanyl-5,8-bis(oxidanylidene)-2,3-dihydro-1~{H}-pyrrolo[1,2-a]indol-4-yl]methyl carbamate (3 entities in total) |
| Functional Keywords | sam-dependent methyltransferase, transferase |
| Biological source | Streptomyces caespitosus |
| Total number of polymer chains | 2 |
| Total formula weight | 64960.37 |
| Authors | |
| Primary citation | 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., 2026 Cited by 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: 42057505DOI: 10.1021/jacs.6c02250 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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