2XEM

Induced-fit and allosteric effects upon polyene binding revealed by crystal structures of the Dynemicin thioesterase

2XEM の概要

• エントリーDOI: 10.2210/pdb2xem/pdb
• 関連するPDBエントリー: 2XFL
• 分子名称: DYNE7, (3E,5E,7E,9E,11E,13E)-pentadeca-3,5,7,9,11,13-hexaen-2-one (3 entities in total)
• 機能のキーワード: biosynthetic protein, polyketide biosynthesis, enediyne antitumor agent, thioesterase
• 由来する生物種: MICROMONOSPORA CHERSINA
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 67963.23

構造登録者

Liew, C.W.,Sharff, A.,Kotaka, M.,Kong, R.,Bricogne, G.,Liang, Z.X.,Lescar, J. (登録日: 2010-05-17, 公開日: 2010-10-13, 最終更新日: 2023-12-20)

主引用文献

Liew, C.W.,Sharff, A.,Kotaka, M.,Kong, R.,Sun, H.,Qureshi, I.,Bricogne, G.,Liang, Z.X.,Lescar, J.
Induced-Fit Upon Ligand Binding Revealed by Crystal Structures of the Hot-Dog Fold Thioesterase in Dynemicin Biosynthesis.
J.Mol.Biol., 404:291-, 2010

PubMed Abstract: Dynemicins are structurally related 10-membered enediyne natural products isolated from Micromonospora chernisa with potent antitumor and antibiotic activity. The early biosynthetic steps of the enediyne moiety of dynemicins are catalyzed by an iterative polyketide synthase (DynE8) and a thioesterase (DynE7). Recent studies indicate that the function of DynE7 is to off-load the linear biosynthetic intermediate assembled on DynE8. Here, we report crystal structures of DynE7 in its free form at 2.7 Å resolution and of DynE7 in complex with the DynE8-produced all-trans pentadecen-2-one at 2.1 Å resolution. These crystal structures reveal that upon ligand binding, significant conformational changes throughout the substrate-binding tunnel result in an expanded tunnel that traverses an entire monomer of the tetrameric DynE7 protein. The enlarged inner segment of the channel binds the carbonyl-conjugated polyene mainly through hydrophobic interactions, whereas the putative catalytic residues are located in the outer segment of the channel. The crystallographic information reinforces an unusual catalytic mechanism that involves a strictly conserved arginine residue for this subfamily of hot-dog fold thioesterases, distinct from the typical mechanism for hot-dog fold thioesterases that utilizes an acidic residue for catalysis.

PubMed: 20888341
DOI: 10.1016/J.JMB.2010.09.041

実験手法

X-RAY DIFFRACTION (2.1 Å)