6O9P
Wild-type SaSQS1 Complexed with Ibandronate
Summary for 6O9P
| Entry DOI | 10.2210/pdb6o9p/pdb |
| Descriptor | Sesquisabinene B synthase 1, IBANDRONATE, 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | terpene, cyclase, sesquisabinene, ibandronate, lyase |
| Biological source | Santalum album (White sandalwood) |
| Total number of polymer chains | 1 |
| Total formula weight | 66059.42 |
| Authors | Blank, P.N.,Christianson, D.W. (deposition date: 2019-03-14, release date: 2019-04-03, Last modification date: 2023-10-11) |
| Primary citation | Blank, P.N.,Shinsky, S.A.,Christianson, D.W. Structure of Sesquisabinene Synthase 1, a Terpenoid Cyclase That Generates a Strained [3.1.0] Bridged-Bicyclic Product. Acs Chem.Biol., 14:1011-1019, 2019 Cited by PubMed Abstract: The natural product sesquisabinene is a key component of the fragrant essential oil of the sandalwood tree, currently valued at $5,000/L. Sesquisabinene contains a highly strained [3.1.0] bicyclic ring system and is generated from farnesyl diphosphate in a reaction catalyzed by a class I terpenoid cyclase. To understand how the enzyme directs the formation of a strained hydrocarbon ring system, we now report the X-ray crystal structure of sesquisabinene synthase 1 (SQS1) from the Indian sandalwood tree ( Santalum album). Specifically, we report the structure of unliganded SQS1 at 1.90 Å resolution and the structure of its complex with three Mg ions and the inhibitor ibandronate at 2.10 Å resolution. The bisphosphonate group of ibandronate coordinates to all three metal ions and makes hydrogen bond interactions with basic residues at the mouth of the active site. These interactions are similarly required for activation of the substrate diphosphate group to initiate catalysis, although partial occupancy binding of the Mg ion suggests that this structure represents the penultimate metal coordination complex just prior to substrate activation. The structure of the liganded enzyme enables a precise definition of the enclosed active site contour that serves as a template for the cyclization reaction. This contour is very product-like in shape and readily fits an extended conformation of sesquisabinene and its precursor, the homobisabolyl cation. Structural comparisons of SQS1 with epi-isozizaene synthase mutants that also generate sesquisabinene suggest that [3.1.0] ring formation is not dependent on the isoprenoid tail conformation of the homobisabolyl cation. PubMed: 30977996DOI: 10.1021/acschembio.9b00218 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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