9hqi

T-Muurolol Synthase from Roseiflexus castenholzii (TmS) in complex with 2,3-DHFPP [P4(3)2(1)2(1)]

spinqualitylabelsall models 9hqi, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9hqi is a 2 chain structure with sequence from Roseiflexus castenholzii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: 3E9, BU3, EDO, GOL, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TMUUS_ROSCS Catalyzes the conversion of (2E,6E)-farnesyl diphosphate (FPP) into (+)-T-muurolol via a 1,10-cyclization, which requires isomerization of FPP to nerolidyl diphosphate (NPP) and then abstraction of the pyrophosphate from intermediate NPP leading to a (E,Z)-germacradienyl (helminthogermacradienyl) cation. Publication Abstract from PubMed Terpene synthases orchestrate complex cyclization cascades that transform simple polyisoprenoid precursors into structurally diverse natural products, often with exquisite stereochemical control. Here we combine high-resolution X-ray crystallography, site-directed mutagenesis, and QM/MM calculations to dissect the catalytic mechanisms of two bacterial sesquiterpene synthases for T-muurolol (TmS) and 1-epi-cubenol (NcECS). The structures reveal a dynamic transition between open and closed states, controlled by a trinuclear magnesium cluster that mediates substrate binding, carbocation formation, and intramolecular pyrophosphate transfer to generate (R)-nerolidyl pyrophosphate, the precursor to Z-configured products. Using synthetic dihydro-surrogates, we identify a counterclockwise substrate orientation, not previously observed in terpene synthases, and visualize a series of trapped hydrocarbons that resemble several of the proposed cationic intermediates along the cyclization cascade. Complementary quantum chemical calculations support their observed geometries and indicate that the active site can transiently accommodate these intermediate analogs, offering a structural basis for understanding how sesquiterpene synthases guide complex carbocationic pathways. Structural Mimics of Hydrocarbon Intermediates Reveal Counterclockwise Cyclization Pathways in the Sesquiterpene Synthases TmS and NcECS.,Groll M, Li H, Troycke P, Kaila VRI, Dickschat JS J Am Chem Soc. 2025 Dec 10. doi: 10.1021/jacs.5c17732. PMID:41372098 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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