Further Insights on the Datura innoxia Hyoscyamine 6β-Hydroxylase (DiH6H) Based on Biochemical Characterization and Molecular Modeling
| Autor: | Daniel Schlesinger, Rachel Davidovich Rikanati, Ofir Tal, Faris Salama, Mwafaq Ibdah, Efraim Lewinsohn, Mosaab Yahyaa, Adi Faigenboim, Moshe Inbar, Rotem Sertchook |
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| Rok vydání: | 2021 |
| Předmět: |
0106 biological sciences
Modern medicine biology Active site Tropane 04 agricultural and veterinary sciences General Medicine biology.organism_classification 01 natural sciences Anisodamine chemistry.chemical_compound chemistry Biochemistry Datura 040103 agronomy & agriculture medicine biology.protein 0401 agriculture forestry and fisheries Datura metel Hyoscyamine Solanaceae 010606 plant biology & botany medicine.drug |
| Zdroj: | American Journal of Plant Sciences. 12:53-70 |
| ISSN: | 2158-2750 2158-2742 |
| Popis: | Hyoscyamine, anisodamine and scopolamine are tropane alkaloids present in some Solanaceae species and used in modern medicine. L-Hyoscyamine is hydroxylated to 6β-hydroxyhyoscyamine (anisodamine) and then epoxidated to scopolamine by the dual action of hyoscyamine 6β-hydroxylase (H6H), a 2-oxoglutarate dependent dioxygenase. A natural mutation in the Gly-220 residue to Cys was previously shown to be associated with the loss of function of H6H in Mandragora officinarum, preventing the accumulation of anisodamine and scopolamine in these plants. We show here that a deliberate Gly220Cys mutation in the Datura innoxia DiH6H protein caused a loss of both its enzymatic abilities and rendered it unable to hydroxylate L-hyoscyamine into anisodamine and to epoxidate anisodamine into scopolamine. By using protein modeling based on an available crystal structure of H6H from Datura metel, we show how the Cys220 residue causes a steric interference in the active site cavity impairing the interaction of both substrates, hyoscyamine and anisodamine with the active site of the protein. We also address the enantiomeric preference of DiH6H based on molecular modeling. |
| Databáze: | OpenAIRE |
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