22TY

Crystal structure of AstC terpene cyclase domain

22TY の概要

• エントリーDOI: 10.2210/pdb22ty/pdb
• 分子名称: AstC, GLYCEROL, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: haloacid dehalogenase-like terpene cyclase, biosynthetic protein
• 由来する生物種: Aspergillus oryzae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69839.31

構造登録者

Chen, T.-H.,Huang, K.-F.,Ko, T.-P.,Lin, H.-C. (登録日: 2026-01-23, 公開日: 2026-07-29)

主引用文献

Chen, T.H.,Huang, K.F.,Chou, T.H.,Tseng, C.C.,Huang, R.J.,Ko, T.P.,Liang, S.Y.,Chein, R.J.,Lin, H.C.
Dimerization-Dependent Trans-Domain Coupling Enables Intermediate Transfer in Fungal Haloacid Dehalogenase-Like Terpene Cyclases.
J.Am.Chem.Soc., 148:22120-22130, 2026

PubMed Abstract: Drimane-type sesquiterpenes (DTSs) are a widely distributed terpenoid family with diverse and potent bioactivities. Although DTS synthases occur in plants, bacteria, and fungi, they share little sequence identity across kingdoms, obscuring the mechanistic principles that govern drimane scaffold formation and product phosphorylation states. Haloacid dehalogenase (HAD)-like terpene cyclases (TCs), TC domains fused to HAD-like phosphatases, are especially intriguing because they couple cyclization with dephosphorylation, yet how these enzymes control scaffold outcomes and phosphorylation states across kingdoms remains unresolved. Here, we identify the fungal enzyme AacA as a bifunctional albicanoyl monophosphate synthase that catalyzes class II cyclization of farnesyl pyrophosphate, followed by Mg-dependent dephosphorylation. We further determine the X-ray crystal structures of the fungal drim-8-ene-11-yl pyrophosphate synthase AstC, representing the first structures of fungal HAD-like terpene cyclases. These structures capture substrate- and product-mimic states and reveal a head-to-tail homodimer in which the partner HAD-like domain caps the TC active site and positions the pyrophosphate at the intersubunit interface, consistent with -domain intermediate transfer. In addition, phosphate-release kinetics support cross-monomer TC-to-HAD coupling in dimeric AacA. Structure-guided mutagenesis and assays with farnesyl mono- and thiopyrophosphate analogues further define the determinants of product selectivity and the distinct dephosphorylation capacities of these enzymes. These findings expand fungal DTS enzymology and guide TC engineering.

PubMed: 42139319
DOI: 10.1021/jacs.6c04151

実験手法

X-RAY DIFFRACTION (3.45 Å)