3GWZ

Structure of the Mitomycin 7-O-methyltransferase MmcR

Summary for 3GWZ

• Entry DOI: 10.2210/pdb3gwz/pdb
• Related: 3GXO
• Descriptor: MmcR, CALCIUM ION, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (5 entities in total)
• Functional Keywords: methyltransferase, mitomycin, mmcr, s-adenosyl methionine, transferase
• Biological source: Streptomyces lavendulae
• Total number of polymer chains: 4
• Total formula weight: 162467.81

Authors

Singh, S.,Chang, A.,Bingman, C.A.,Phillips Jr., G.N.,Thorson, J.S. (deposition date: 2009-04-01, release date: 2010-04-07, Last modification date: 2024-11-20)

Primary citation

Singh, S.,Chang, A.,Goff, R.D.,Bingman, C.A.,Gruschow, S.,Sherman, D.H.,Phillips, G.N.,Thorson, J.S.
Structural characterization of the mitomycin 7-O-methyltransferase.
Proteins, 79:2181-2188, 2011

PubMed 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.

PubMed: 21538548
DOI: 10.1002/prot.23040

Experimental method

X-RAY DIFFRACTION (1.91 Å)