Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shi R, Lamb SS, Zakeri B, Proteau A, Cui Q, Sulea T, Matte A, Wright GD, Cygler M. Structure and function of the glycopeptide N-methyltransferase MtfA, a tool for the biosynthesis of modified glycopeptide antibiotics. Chem Biol. 2009 Apr 24;16(4):401-10. PMID:19389626 doi:10.1016/j.chembiol.2009.02.007