PMID:21538548

Citation	Singh, S, Chang, A, Goff, RD, Bingman, CA, Grüschow, S, Sherman, DH, Phillips, GN Jr and Thorson, JS (2011) Structural characterization of the mitomycin 7-O-methyltransferase. Proteins 79:2181-8
Abstract	Mitomycins are quinone-containing antibiotics, widely used as antitumor drugs in chemotherapy. Mitomycin-7-O-methyltransferase (MmcR), a key tailoring enzyme involved in the biosynthesis of mitomycin in Streptomyces lavendulae, catalyzes the 7-O-methylation of both C9β- and C9α-configured 7-hydroxymitomycins. We have determined the crystal structures of the MmcR-S-adenosylhomocysteine (SAH) binary complex and MmcR-SAH-mitomycin A (MMA) ternary complex at resolutions of 1.9and 2.3 Å, respectively. The study revealed MmcR to adopt a common S-adenosyl-L-methionine-dependent O-methyltransferase fold and the presence of a structurally conserved active site general acid-base pair is consistent with a proton-assisted methyltransfer common to most methyltransferases. Given the importance of C7 alkylation to modulate mitomycin redox potential, this study may also present a template toward the future engineering of catalysts to generate uniquely bioactive mitomycins.
Links	PubMed PMC3115387 Online version:10.1002/prot.23040
Keywords	Amino Acid Sequence; Bacterial Proteins; Binding Sites; Crystallography, X-Ray; Methyltransferases/chemistry; Methyltransferases/metabolism; Mitomycin/chemistry; Mitomycin/metabolism; Models, Molecular; Molecular Sequence Data; Protein Binding; Protein Folding; Protein Structure, Tertiary; Recombinant Proteins/chemistry; Recombinant Proteins/metabolism; S-Adenosylhomocysteine/chemistry; S-Adenosylhomocysteine/metabolism; Sequence Alignment; Streptomyces/enzymology; Structural Homology, Protein
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