3g2m

Crystal Structure of the Glycopeptide N-methyltransferase MtfA

spinqualitylabelsall models 3g2m, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3g2m is a 2 chain structure with sequence from "streptomyces_orientalis"_pittenger_and_brigham_1956 "streptomyces orientalis" pittenger and brigham 1956. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: MSE Related: 3g2o, 3g2p, 3g2q Gene: mtfA ("Streptomyces orientalis" Pittenger and Brigham 1956) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 There is a considerable interest in the modification of existing antibiotics to generate new antimicrobials. Glycopeptide antibiotics (GPAs) are effective against serious Gram-positive bacterial pathogens including methicillin-resistant Staphylococcus aureus. However, resistance to these antibiotics is becoming a serious problem requiring new strategies. We show that the Amycolatopsis orientalis (S)-adenosyl-L-methionine-dependent methyltransferase MtfA, from the vancomycin-class GPA chloroeremomycin biosynthetic pathway, catalyzes in vivo and in vitro methyl transfer to generate methylated GPA derivatives of the teicoplanin class. The crystal structure of MtfA complexed with (S)-adenosyl-L-methionine, (S)-adenosylhomocysteine, or sinefungin inhibitor, coupled with mutagenesis, identified His228 as a likely general base required for methyl transfer to the N terminus of the glycopeptide. Computational docking and molecular dynamics simulations were used to model binding of demethyl-vancomycin aglycone to MtfA. These results demonstrate its utility as a tool for engineering methylated analogs of GPAs. Structure and function of the glycopeptide N-methyltransferase MtfA, a tool for the biosynthesis of modified glycopeptide antibiotics.,Shi R, Lamb SS, Zakeri B, Proteau A, Cui Q, Sulea T, Matte A, Wright GD, Cygler M Chem Biol. 2009 Apr 24;16(4):401-10. PMID:19389626 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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