2WDW

The Native Crystal Structure of the Primary Hexose Oxidase (Dbv29) in Antibiotic A40926 Biosynthesis

2WDW の概要

• エントリーDOI: 10.2210/pdb2wdw/pdb
• 関連するPDBエントリー: 2WDX
• 分子名称: PUTATIVE HEXOSE OXIDASE, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: fad, flavoprotein, hexose oxidase, oxidoreductase
• 由来する生物種: NONOMURAEA SP. ATCC 39727
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 115689.12

構造登録者

Liu, Y.-C.,Li, Y.-S.,Lyu, S.-Y.,Chen, Y.-H.,Chan, H.-C.,Huang, C.-J.,Huang, Y.-T.,Chen, G.-H.,Chou, C.-C.,Tsai, M.-D.,Li, T.-L. (登録日: 2009-03-27, 公開日: 2010-04-07, 最終更新日: 2024-10-23)

主引用文献

Liu, Y.-C.,Li, Y.-S.,Lyu, S.-Y.,Hsu, L.-J.,Chen, Y.-H.,Huang, Y.-T.,Chan, H.-C.,Huang, C.-J.,Chen, G.-H.,Chou, C.-C.,Tsai, M.-D.,Li, T.-L.
Interception of Teicoplanin Oxidation Intermediates Yields New Antimicrobial Scaffolds
Nat.Chem.Biol., 7:304-, 2011

PubMed Abstract: In the search for new efficacious antibiotics, biosynthetic engineering offers attractive opportunities to introduce minor alterations to antibiotic structures that may overcome resistance. Dbv29, a flavin-containing oxidase, catalyzes the four-electron oxidation of a vancomycin-like glycopeptide to yield A40926. Structural and biochemical examination of Dbv29 now provides insights into residues that govern flavinylation and activity, protein conformation and reaction mechanism. In particular, the serendipitous discovery of a reaction intermediate in the crystal structure led us to identify an unexpected opportunity to intercept the normal enzyme mechanism at two different points to create new teicoplanin analogs. Using this method, we synthesized families of antibiotic analogs with amidated and aminated lipid chains, some of which showed marked potency and efficacy against multidrug resistant pathogens. This method offers a new strategy for the development of chemical diversity to combat antibacterial resistance.

PubMed: 21478878
DOI: 10.1038/NCHEMBIO.556

実験手法

X-RAY DIFFRACTION (3.21 Å)