Structural characterization of the mitomycin 7-O-methyltransferase
- Michigan
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 C9{beta}- and C9{alpha}-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 1.9 and 2.3 {angstrom}, 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.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- DOE - BASIC ENERGY SCIENCESNIHOTHER U.S. STATESNCINIGMS
- OSTI ID:
- 1024046
- Journal Information:
- Proteins, Vol. 79, Issue (7) ; 07, 2011; ISSN 0887-3585
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
Crystallization and preliminary X-ray analysis of the O-methyltransferase NovP from the novobiocin-biosynthetic cluster of Streptomyces spheroides
A New Structural Form in the SAM/Metal-Dependent O;#8209;Methyltransferase Family: MycE from the Mycinamicin Biosynthetic Pathway