3gxo

Structure of the Mitomycin 7-O-methyltransferase MmcR with bound Mitomycin A

spinqualitylabelsall models 3gxo, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3gxo is a 4 chain structure with sequence from Streptomyces lavendulae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: CA, MQA, MSE, SAH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MMCR_STRLA Involved in the biosynthesis of the quinone methoxy group present in the mitomycin A and B, which are used as anticancer agents (PubMed:10099135, PubMed:17461583). In vitro, catalyzes the 6-O-methylation of both C9-beta- and C9-alpha-configured 6-hydroxymitomycins via the transfer of the S-methyl group of S-adenosyl-L-methionine (AdoMet) to the 6-demethylmitomycin A and B. It can also use hydroxyquinone as substrate (PubMed:17461583). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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 C9beta- and C9alpha-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 A, 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. Proteins 2011. (c) 2011 Wiley-Liss, Inc. Structural characterization of the mitomycin 7-O-methyltransferase.,Singh S, Chang A, Goff RD, Bingman CA, Gruschow S, Sherman DH, Phillips GN Jr, Thorson JS Proteins. 2011 Mar 22. doi: 10.1002/prot.23040. PMID:21538548 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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