AI Article Synopsis
- Hyoscyamine 6β-hydroxylase (H6H) is an enzyme that plays a key role in the last two steps of scopolamine production, using iron and oxygen in its reaction.
- High-resolution crystal structures of H6H from Datura metel revealed how it binds to its substrate and highlighted the important roles of two amino acids, Glu-116 and Tyr-326, in the enzymatic process.
- Computational calculations were performed to understand why hydroxylation occurs at specific carbon positions on hyoscyamine, with results indicating the contributions of different active site residues to the reaction's energy barriers.
Article Abstract
Hyoscyamine 6β-hydroxylase (H6H) is a bifunctional non-heme 2-oxoglutarate/Fe2+-dependent dioxygenase that catalyzes the two final steps in the biosynthesis of scopolamine. Based on high resolution crystal structures of H6H from Datura metel, detailed information on substrate binding was obtained that provided insights into the onset of the enzymatic process. In particular, the role of two prominent residues was revealed - Glu-116 that interacts with the tertiary amine located on the hyoscyamine tropane moiety and Tyr-326 that forms CH-π hydrogen bonds with the hyoscyamine phenyl ring. The structures were used as the basis for QM/MM calculations that provided an explanation for the regioselectivity of the hydroxylation reaction on the hyoscyamine tropane moiety (C6 vs. C7) and quantified contributions of active site residues to respective barrier heights.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9705211 | PMC |
| http://dx.doi.org/10.1039/d0dt00302f | DOI Listing |
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