Regioselectivity of hyoscyamine 6ß-hydroxylase-catalysed hydroxylation as revealed by high-resolution structural information and QM/MM calculations.
Dalton Trans
; 49(14): 4454-4469, 2020 Apr 07.
Article
em En
| MEDLINE
| ID: mdl-32182320
ABSTRACT
Hyoscyamine 6ß-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Teoria Quântica
/
Escopolamina
/
Oxigenases de Função Mista
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article