8H72
Class I sesquiterpene synthase DbPROS (complex)
Summary for 8H72
| Entry DOI | 10.2210/pdb8h72/pdb |
| Descriptor | Delta(6)-protoilludene synthase K435DRAFT_659367, MAGNESIUM ION, N-benzyl-N,N-diethylethanaminium, ... (4 entities in total) |
| Functional Keywords | class i sesquiterpene synthase dbpros (complex), structural protein |
| Biological source | Dendrothele bispora (strain CBS 962.96) |
| Total number of polymer chains | 2 |
| Total formula weight | 83332.83 |
| Authors | |
| Primary citation | Lou, T.,Li, A.,Xu, H.,Pan, J.,Xing, B.,Wu, R.,Dickschat, J.S.,Yang, D.,Ma, M. Structural Insights into Three Sesquiterpene Synthases for the Biosynthesis of Tricyclic Sesquiterpenes and Chemical Space Expansion by Structure-Based Mutagenesis. J.Am.Chem.Soc., 2023 Cited by PubMed Abstract: The cyclization of farnesyl diphosphate (FPP) into highly strained polycyclic sesquiterpenes is challenging. We here determined the crystal structures of three sesquiterpene synthases (STSs, namely, BcBOT2, DbPROS, and CLM1) catalyzing the biosynthesis of the tricyclic sesquiterpenes presilphiperfolan-8β-ol (), Δ-protoilludene (), and longiborneol (). All three STS structures contain a substrate mimic, the benzyltriethylammonium cation (BTAC), in their active sites, providing ideal templates for quantum mechanics/molecular mechanics (QM/MM) analyses toward their catalytic mechanisms. The QM/MM-based molecular dynamics (MD) simulations revealed the cascade reactions toward the enzyme products, and different key active site residues that play important roles in stabilizing reactive carbocation intermediates along the three pathways. Site-directed mutagenesis experiments confirmed the roles of these key residues and concomitantly resulted in 17 shunt products (-). Isotopic labeling experiments addressed the key hydride and methyl migrations toward the main and several shunt products. These combined methods provided deep insights into the catalytic mechanisms of the three STSs and demonstrated how the chemical space of STSs can rationally be expanded, which may facilitate applications in synthetic biology approaches toward pharmaceutical and perfumery agents. PubMed: 37018048DOI: 10.1021/jacs.3c00278 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.09 Å) |
Structure validation
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