8B25

Dihydroprecondylocarpine acetate synthase 2 from Tabernanthe iboga - stemmadenine acetate bound structure

Summary for 8B25

• Entry DOI: 10.2210/pdb8b25/pdb
• Descriptor: Dihydroprecondylocarpine acetate synthase 2, stemmadenine acetate, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: alcohol dehydrogenase, cytosolic protein
• Biological source: Tabernanthe iboga
• Total number of polymer chains: 2
• Total formula weight: 79988.48

Authors

Langley, C.,Basquin, J.,Caputi, L.,O'Connor, S.E. (deposition date: 2022-09-13, release date: 2022-10-19, Last modification date: 2024-01-31)

Primary citation

Langley, C.,Tatsis, E.,Hong, B.,Nakamura, Y.,Paetz, C.,Stevenson, C.E.M.,Basquin, J.,Lawson, D.M.,Caputi, L.,O'Connor, S.E.
Expansion of the Catalytic Repertoire of Alcohol Dehydrogenases in Plant Metabolism.
Angew.Chem.Int.Ed.Engl., 61:e202210934-e202210934, 2022

PubMed Abstract: Medium-chain alcohol dehydrogenases (ADHs) comprise a highly conserved enzyme family that catalyse the reversible reduction of aldehydes. However, recent discoveries in plant natural product biosynthesis suggest that the catalytic repertoire of ADHs has been expanded. Here we report the crystal structure of dihydroprecondylocarpine acetate synthase (DPAS), an ADH that catalyses the non-canonical 1,4-reduction of an α,β-unsaturated iminium moiety. Comparison with structures of plant-derived ADHs suggest the 1,4-iminium reduction does not require a proton relay or the presence of a catalytic zinc ion in contrast to canonical 1,2-aldehyde reducing ADHs that require the catalytic zinc and a proton relay. Furthermore, ADHs that catalysed 1,2-iminium reduction required the presence of the catalytic zinc and the loss of the proton relay. This suggests how the ADH active site can be modified to perform atypical carbonyl reductions, providing insight into how chemical reactions are diversified in plant metabolism.

PubMed: 36198083
DOI: 10.1002/anie.202210934

Experimental method

X-RAY DIFFRACTION (2.24 Å)