5BU3

Crystal Structure of Diels-Alderase PyrI4 in complex with its product

5BU3 の概要

• エントリーDOI: 10.2210/pdb5bu3/pdb
• 関連するPDBエントリー: 5BTU
• 分子名称: PyrI4, GLYCEROL, (4S,4aS,6aS,8R,9R,10aR,13R,14aS,18aR,18bR)-9-ethyl-4,8,19-trihydroxy-10a,12,13,18a-tetramethyl-2,3,4,4a,5,6,6a,7,8,9,10,10a,13,14,18a,18b-hexadecahydro-1H-14a,17-(metheno)benzo[b]naphtho[2,1-h]azacyclododecine-16,18(15H,17H)-dione, ... (4 entities in total)
• 機能のキーワード: diels-alderase, complex, lyase
• 由来する生物種: Streptomyces rugosporus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 80731.98

構造登録者

Pan, L.,Guo, Y.,Liu, J. (登録日: 2015-06-03, 公開日: 2016-02-24, 最終更新日: 2023-11-08)

主引用文献

Zheng, Q.,Guo, Y.,Yang, L.,Zhao, Z.,Wu, Z.,Zhang, H.,Liu, J.,Cheng, X.,Wu, J.,Yang, H.,Jiang, H.,Pan, L.,Liu, W.
Enzyme-Dependent [4 + 2] Cycloaddition Depends on Lid-like Interaction of the N-Terminal Sequence with the Catalytic Core in PyrI4
Cell Chem Biol, 23:352-360, 2016

PubMed Abstract: The Diels-Alder [4 + 2] cycloaddition reaction is one of the most powerful and elegant organic synthesis methods for forming 6-membered molecules and has been known for nearly a century. However, whether and how enzymes catalyze this type of reaction is still not completely clear. Here we focus on PyrI4, an enzyme found in the biosynthetic pathway of pyrroindomycins where it catalyzes the formation of a spiro-conjugate via an enzyme-dependent exo-selective [4 + 2] cycloaddition reaction. We report the crystal structures of PyrI4 alone and in complex with its product. Comparative analysis of these structures, combined with biochemical analysis, lead us to propose a unique trapping mechanism whereby the lid-like action of the N-terminal tail imposes conformational constraints on the β barrel catalytic core, which enhances the proximity and polarization effects of reactive groups (1,3-diene and alkene) to drive cyclization in a regio- and stereo-specific manner. This work represents an important step toward the wider application of enzyme-catalyzed [4 + 2] cyclization for synthetic purposes.

PubMed: 26877021
DOI: 10.1016/j.chembiol.2016.01.005

実験手法

X-RAY DIFFRACTION (1.897 Å)