6KA3

Crystal structure of a Thebaine synthase from Papaver somniferum

Summary for 6KA3

• Entry DOI: 10.2210/pdb6ka3/pdb
• Descriptor: Thebaine synthase 2, SULFATE ION, PALMITIC ACID, ... (4 entities in total)
• Functional Keywords: synthase, crystallization, biosynthetic protein
• Biological source: Papaver somniferum (Opium poppy)
• Total number of polymer chains: 4
• Total formula weight: 73070.11

Authors

Xue, J.,Yu, X.J.,Huang, J.W.,Liu, W.D.,Chen, C.C.,Guo, R.T. (deposition date: 2019-06-20, release date: 2020-06-24, Last modification date: 2024-10-23)

Primary citation

Chen, C.C.,Xue, J.,Peng, W.,Wang, B.,Zhang, L.,Liu, W.,Ko, T.P.,Huang, J.W.,Zhou, S.,Min, J.,Ma, L.,Dai, L.,Guo, R.T.,Yu, X.
Structural insights into thebaine synthase 2 catalysis.
Biochem.Biophys.Res.Commun., 529:156-161, 2020

PubMed Abstract: Thebaine synthase 2 (THS2) that can transform (7S)-salutaridinol 7-O-acetate to thebaine catalyzes the final step of thebaine biosynthesis in Papaver somniferum. Here, the crystal structures of THS2 and its complex with thebaine are reported, revealing the interaction network in the substrate-binding pocket. Subsequent docking and QM/MM studies was performed to further explore the catalytic mechanism of THS2. Our results suggest that T105 may abstract the proton of C4-OH from the substrate under the assistance of H89. The resulting C4-O phenolate anion then attacks the nearby C5, and triggers intramolecular S2' syn displacement with the elimination of O-acetyl group. Moreover, the latter S2' reaction is the rate-determining step of the whole enzymatic reaction with an overall energy barrier of 18.8 kcal/mol. These findings are of pivotal importance to understand the mechanism of action of thebaine biosynthesis, and would guide enzyme engineering to enhance the production of opiate alkaloids via metabolic engineering.

PubMed: 32703404
DOI: 10.1016/j.bbrc.2020.05.199

Experimental method

X-RAY DIFFRACTION (1.951 Å)