6TTO

N-terminally truncated hyoscyamine 6-hydroxylase (tH6H) in complex with 2-oxoglutarate

Summary for 6TTO

• Entry DOI: 10.2210/pdb6tto/pdb
• Related: 6TTM 6TTN
• Descriptor: Hyoscyamine 6 beta-hydroxylase, 2-OXOGLUTARIC ACID, 1,2-ETHANEDIOL, ... (8 entities in total)
• Functional Keywords: jelly-roll, non-heme, 2-oxoglutarate, oxidoreductase
• Biological source: Datura metel (Hindu datura)
• Total number of polymer chains: 1
• Total formula weight: 37355.22

Authors

Kluza, A.,Mrugala, B.,Porebski, P.J.,Kurpiewska, K.,Niedzialkowska, E.,Weiss, M.S.,Borowski, T. (deposition date: 2019-12-29, release date: 2020-03-18, Last modification date: 2024-11-06)

Primary citation

Kluza, A.,Wojdyla, Z.,Mrugala, B.,Kurpiewska, K.,Porebski, P.J.,Niedzialkowska, E.,Minor, W.,Weiss, M.S.,Borowski, T.
Regioselectivity of hyoscyamine 6 beta-hydroxylase-catalysed hydroxylation as revealed by high-resolution structural information and QM/MM calculations.
Dalton Trans, 49:4454-4469, 2020

PubMed 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.

PubMed: 32182320
DOI: 10.1039/d0dt00302f

Experimental method

X-RAY DIFFRACTION (1.31 Å)