3G2M

Crystal Structure of the Glycopeptide N-methyltransferase MtfA

3G2M の概要

• エントリーDOI: 10.2210/pdb3g2m/pdb
• 関連するPDBエントリー: 3G2O 3G2P 3G2Q
• 分子名称: PCZA361.24 (2 entities in total)
• 機能のキーワード: sam-dependent methyltransferase, glycopeptide antibiotics biosynthesis, structural genomics, montreal-kingston bacterial structural genomics initiative, bsgi, transferase
• 由来する生物種: Amycolatopsis orientalis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65711.77

構造登録者

Shi, R.,Matte, A.,Cygler, M.,Montreal-Kingston Bacterial Structural Genomics Initiative (BSGI) (登録日: 2009-01-31, 公開日: 2009-05-05, 最終更新日: 2024-11-27)

主引用文献

Shi, R.,Lamb, S.S.,Zakeri, B.,Proteau, A.,Cui, Q.,Sulea, T.,Matte, A.,Wright, G.D.,Cygler, M.
Structure and function of the glycopeptide N-methyltransferase MtfA, a tool for the biosynthesis of modified glycopeptide antibiotics.
Chem.Biol., 16:401-410, 2009

PubMed Abstract: 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.

PubMed: 19389626
DOI: 10.1016/j.chembiol.2009.02.007

実験手法

X-RAY DIFFRACTION (2 Å)