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Title | Structural basis of the Meinwald rearrangement catalysed by styrene oxide isomerase. |
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Journal, issue, pages | Nat Chem, Year 2024 |
Publish date | May 14, 2024 |
Authors | Basavraj Khanppnavar / Joel P S Choo / Peter-Leon Hagedoorn / Grigory Smolentsev / Saša Štefanić / Selvapravin Kumaran / Dirk Tischler / Fritz K Winkler / Volodymyr M Korkhov / Zhi Li / Richard A Kammerer / Xiaodan Li / |
PubMed Abstract | Membrane-bound styrene oxide isomerase (SOI) catalyses the Meinwald rearrangement-a Lewis-acid-catalysed isomerization of an epoxide to a carbonyl compound-and has been used in single and cascade ...Membrane-bound styrene oxide isomerase (SOI) catalyses the Meinwald rearrangement-a Lewis-acid-catalysed isomerization of an epoxide to a carbonyl compound-and has been used in single and cascade reactions. However, the structural information that explains its reaction mechanism has remained elusive. Here we determine cryo-electron microscopy (cryo-EM) structures of SOI bound to a single-domain antibody with and without the competitive inhibitor benzylamine, and elucidate the catalytic mechanism using electron paramagnetic resonance spectroscopy, functional assays, biophysical methods and docking experiments. We find ferric haem b bound at the subunit interface of the trimeric enzyme through H58, where Fe(III) acts as the Lewis acid by binding to the epoxide oxygen. Y103 and N64 and a hydrophobic pocket binding the oxygen of the epoxide and the aryl group, respectively, position substrates in a manner that explains the high regio-selectivity and stereo-specificity of SOI. Our findings can support extending the range of epoxide substrates and be used to potentially repurpose SOI for the catalysis of new-to-nature Fe-based chemical reactions. |
External links | Nat Chem / PubMed:38744914 |
Methods | EM (single particle) |
Resolution | 2.048 - 2.12 Å |
Structure data | EMDB-17785, PDB-8pnu: EMDB-17786, PDB-8pnv: |
Chemicals | ChemComp-ABN: ChemComp-HEM: ChemComp-HOH: |
Source |
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Keywords | MEMBRANE PROTEIN / Heme binding protein / Enzyme / Isomerase |