Crystal structure of LepI, a multifunctional SAM-dependent enzyme which catalyzes pericyclic reactions in leporin biosynthesis
| Autor: | Yong Yang, Chun-Chi Chen, Zhenying Chang, Guimin Zhang, Dan Thomas Major, Jian-Wen Huang, Tamar Ansbacher, Longhai Dai, Lilan Zhang, Weidong Liu, Rey-Ting Guo, Tzu Ping Ko |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pericyclic reaction S-Adenosylmethionine Stereochemistry Protein Conformation Pyridones Stereoisomerism 010402 general chemistry Crystallography X-Ray 01 natural sciences Biochemistry Aspergillus nidulans Catalysis Fungal Proteins 03 medical and health sciences Protein structure Tetramer Catalytic Domain Molecule Benzopyrans Amino Acid Sequence Physical and Theoretical Chemistry Alkyl chemistry.chemical_classification Cycloaddition Reaction Chemistry Organic Chemistry 0104 chemical sciences Biosynthetic Pathways Molecular Docking Simulation 030104 developmental biology Docking (molecular) Protein Multimerization |
| Zdroj: | Organicbiomolecular chemistry. 17(8) |
| ISSN: | 1477-0539 |
| Popis: | LepI is a novel multifunctional enzyme that catalyzes stereoselective dehydration, Diels-Alder reaction, and retro-Claisen rearrangement. Here we report the crystal structure of LepI in complex with its co-factor S-adenosyl methionine (SAM). LepI forms a tetramer via the N-terminal helical domain and binds to a SAM molecule in the C-terminal catalytic domain. The binding modes of various LepI substrates are investigated by docking simulations, which suggest that the substrates are bound via both hydrophobic and hydrophilic forces, as well as cation-π interactions with the positively charged SAM. The reaction starts with a dehydration step in which H133 possibly deprotonates the pyridone hydroxyl group of the substrate, while D296 might protonate an alkyl-chain hydroxyl group. Subsequent pericyclization may be facilitated by the correct fold of the substrate's alkyl chain and a thermodynamic driving force towards σ-bonds at the expense of π-bonds. These results provide structural insights into LepI catalysis and are important in understanding the mechanism of enzymatic pericyclization. |
| Databáze: | OpenAIRE |
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