9LPB

Terpene cyclase AriE mutant-D128A

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9LPB の概要

• エントリーDOI: 10.2210/pdb9lpb/pdb
• 分子名称: Terpene synthase (2 entities in total)
• 機能のキーワード: cis-eunicellane cyclase, metal binding protein
• 由来する生物種: Amycolatopsis arida
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42459.11

構造登録者

Li, F.R.,Yang, Q.,He, J.Y.,Sun, X.R.,Pan, X.M.,Xu, H.M.,Rudolf, J.D.,Dong, L.B. (登録日: 2025-01-24, 公開日: 2025-05-07)

主引用文献

Li, F.R.,Yang, Q.,He, J.,Sun, X.,Pan, X.,Xu, H.M.,Rudolf, J.D.,Dong, L.B.
Crystal Structure and Catalytic Mechanism of the cis-Eunicellane Cyclase AriE.
Chemistry, :e202500012-e202500012, 2025

PubMed Abstract: Eunicellane diterpenoids, with over 360 known examples characterized by a cis- or trans-6/10-bicyclic carbon skeleton, exhibit diverse biological activities. To date, five eunicellane cyclases (ECs) have been reported: cis-ECs (Bnd4, CpDTS2 and EcTPS1) and trans-ECs (AlbS and MicA), yet the structural basis and molecular mechanisms governing their distinct cis- or trans-cyclization modes remain unsolved. Here, we present the crystal structure of a cis-EC AriE from Amycolatopsis arida, which catalyzes geranylgeranyl diphosphate to form cis-6/10-fused bicyclic benditerpe-2,6,15-triene (1) in aridacin biosynthesis. Through surface entropy reduction, we obtained the 1.87 Å resolution structure of AriED128A. Structure-guided mutagenesis identified W73 as a key regulatory hotspot controlling product diversity, with its variants generating diverse diterpene products. Y203A converted AriE into a highly specific (-)-(R)-cembrene A synthase. Our findings provide the first structural insights into this type of terpene synthase and demonstrate the feasibility of engineering EC variants for selective product formation.

PubMed: 40265331
DOI: 10.1002/chem.202500012

実験手法

X-RAY DIFFRACTION (1.87 Å)