3gxo

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

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:	, , ,
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).^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mao Y, Varoglu M, Sherman DH. Molecular characterization and analysis of the biosynthetic gene cluster for the antitumor antibiotic mitomycin C from Streptomyces lavendulae NRRL 2564. Chem Biol. 1999 Apr;6(4):251-63. PMID:10099135 doi:10.1016/S1074-5521(99)80040-4
↑ Grüschow S, Chang LC, Mao Y, Sherman DH. Hydroxyquinone O-methylation in mitomycin biosynthesis. J Am Chem Soc. 2007 May 23;129(20):6470-6. PMID:17461583 doi:10.1021/ja0700193
↑ Singh S, Chang A, Goff RD, Bingman CA, Gruschow S, Sherman DH, Phillips GN Jr, Thorson JS. Structural characterization of the mitomycin 7-O-methyltransferase. Proteins. 2011 Mar 22. doi: 10.1002/prot.23040. PMID:21538548 doi:10.1002/prot.23040

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OCA

[1] Mao Y, Varoglu M, Sherman DH. Molecular characterization and analysis of the biosynthetic gene cluster for the antitumor antibiotic mitomycin C from Streptomyces lavendulae NRRL 2564. Chem Biol. 1999 Apr;6(4):251-63. PMID:10099135 doi:10.1016/S1074-5521(99)80040-4

[2] Grüschow S, Chang LC, Mao Y, Sherman DH. Hydroxyquinone O-methylation in mitomycin biosynthesis. J Am Chem Soc. 2007 May 23;129(20):6470-6. PMID:17461583 doi:10.1021/ja0700193

[3] Singh S, Chang A, Goff RD, Bingman CA, Gruschow S, Sherman DH, Phillips GN Jr, Thorson JS. Structural characterization of the mitomycin 7-O-methyltransferase. Proteins. 2011 Mar 22. doi: 10.1002/prot.23040. PMID:21538548 doi:10.1002/prot.23040

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