2Y08

Structure of the substrate-free FAD-dependent tirandamycin oxidase TamL

2Y08 の概要

• エントリーDOI: 10.2210/pdb2y08/pdb
• 関連するPDBエントリー: 2Y3R 2Y3S 2Y4G
• 分子名称: TAML, FLAVIN-ADENINE DINUCLEOTIDE, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: oxidoreductase
• 由来する生物種: STREPTOMYCES SP. 307-9
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 118806.79

構造登録者

Carlson, J.C.,Li, S.,Gunatilleke, S.S.,Anzai, Y.,Burr, D.A.,Podust, L.M.,Sherman, D.H. (登録日: 2010-11-30, 公開日: 2011-06-29, 最終更新日: 2024-11-06)

主引用文献

Carlson, J.C.,Li, S.,Gunatilleke, S.S.,Anzai, Y.,Burr, D.A.,Podust, L.M.,Sherman, D.H.
Tirandamycin Biosynthesis is Mediated by Co-Dependent Oxidative Enzymes
Nat.Chem, 3:628-, 2011

PubMed Abstract: Elucidation of natural product biosynthetic pathways provides important insights into the assembly of potent bioactive molecules, and expands access to unique enzymes able to selectively modify complex substrates. Here, we show full reconstitution, in vitro, of an unusual multi-step oxidative cascade for post-assembly-line tailoring of tirandamycin antibiotics. This pathway involves a remarkably versatile and iterative cytochrome P450 monooxygenase (TamI) and a flavin adenine dinucleotide-dependent oxidase (TamL), which act co-dependently through the repeated exchange of substrates. TamI hydroxylates tirandamycin C (TirC) to generate tirandamycin E (TirE), a previously unidentified tirandamycin intermediate. TirE is subsequently oxidized by TamL, giving rise to the ketone of tirandamycin D (TirD), after which a unique exchange back to TamI enables successive epoxidation and hydroxylation to afford, respectively, the final products tirandamycin A (TirA) and tirandamycin B (TirB). Ligand-free, substrate- and product-bound crystal structures of bicovalently flavinylated TamL oxidase reveal a likely mechanism for the C10 oxidation of TirE.

PubMed: 21778983
DOI: 10.1038/NCHEM.1087

実験手法

X-RAY DIFFRACTION (1.7 Å)