29MU
Sesterterpene Synthase from Streptomyces mobaraensis (Sestermobaraene Synthase, SmTS1) in complex with pyrophosphate (PPi)
Summary for 29MU
| Entry DOI | 10.2210/pdb29mu/pdb |
| Related | 9RS2 |
| Descriptor | Glutamate dehydrogenase/leucine dehydrogenase, MAGNESIUM ION, PYROPHOSPHATE 2-, ... (5 entities in total) |
| Functional Keywords | type i terpene synthases, terpene cyclization mechanism, carbocation cascade, enzyme engineering, active site mutagenesis, chemodiversity, lyase |
| Biological source | Streptomyces mobaraensis |
| Total number of polymer chains | 6 |
| Total formula weight | 242050.35 |
| Authors | Troycke, P.,Li, H.,Yang, K.,Dickschat, J.S.,Groll, M. (deposition date: 2026-03-23, release date: 2026-04-08, Last modification date: 2026-09-16) |
| Primary citation | Troycke, P.,Li, H.,Yang, K.,Dickschat, J.S.,Groll, M. Local Active-Site Architecture Directs Divergent Carbocation Cascades in Sesterterpene Synthases. J.Am.Chem.Soc., 148:36648-36661, 2026 Cited by PubMed Abstract: Type I terpene synthases generate complex polycyclic scaffolds through carbocation cascades. However, how closely related enzymes convert a common C25 precursor to distinct sesterterpene frameworks remains unresolved. Here, we combine high-resolution crystal structures with systematic mutagenesis of four bacterial sesterterpene synthases to define the structural basis for pathway divergence. These analyses show how local active-site interactions within a conserved fold redirect carbocation trajectories and thereby control product formation. The structures reveal a preorganized binding mode that positions the substrate in a product-like conformation and directs the cyclization cascade. Comparative structural analyses further support distinct carbocation trajectories involving either centralized cation hubs or sequential rearrangement pathways with the exact pathway being enzyme-dependent. Structure-guided mutagenesis targets these features, alters product profiles, and enables the formation of new terpene scaffolds. Together, crystallographic data and mutagenesis demonstrate that closely related enzymes with the same overall fold can follow distinct carbocation trajectories and reveal how local architectural changes control the cyclization outcome. PubMed: 42701288DOI: 10.1021/jacs.6c06677 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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