22ua

Crystal structure of AstC terpene cyclase domain in complex with albicanoyl monophosphate

spinqualitylabelsall models 22ua, resolution 2.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 22ua is a 2 chain structure with sequence from Aspergillus oryzae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.86Å Ligands: A1MEK, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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(2+)-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 trans-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. Dimerization-Dependent Trans-Domain Coupling Enables Intermediate Transfer in Fungal Haloacid Dehalogenase-Like Terpene Cyclases.,Chen TH, Huang KF, Chou TH, Tseng CC, Huang RJ, Ko TP, Liang SY, Chein RJ, Lin HC J Am Chem Soc. 2026 Jun 3;148(21):22120-22130. doi: 10.1021/jacs.6c04151. Epub , 2026 May 15. PMID:42139319 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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