5L53

Menthone neomenthol reductase from Mentha piperita in complex with NADP

Summary for 5L53

• Entry DOI: 10.2210/pdb5l53/pdb
• Descriptor: (-)-menthone:(+)-neomenthol reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• Functional Keywords: short-chain dehydrogenase/reductases (sdr), rossmann fold, menthone, isomenthone, oxidoreductase
• Biological source: Mentha piperita (Peppermint)
• Total number of polymer chains: 1
• Total formula weight: 36294.42

Authors

Karuppiah, V.,Toogood, H.S.,Leys, D.,Scrutton, N.S. (deposition date: 2016-05-27, release date: 2016-08-31, Last modification date: 2024-01-10)

Primary citation

Lygidakis, A.,Karuppiah, V.,Hoeven, R.,Ni Cheallaigh, A.,Leys, D.,Gardiner, J.M.,Toogood, H.S.,Scrutton, N.S.
Pinpointing a Mechanistic Switch Between Ketoreduction and "Ene" Reduction in Short-Chain Dehydrogenases/Reductases.
Angew.Chem.Int.Ed.Engl., 55:9596-9600, 2016

PubMed Abstract: Three enzymes of the Mentha essential oil biosynthetic pathway are highly homologous, namely the ketoreductases (-)-menthone:(-)-menthol reductase and (-)-menthone:(+)-neomenthol reductase, and the "ene" reductase isopiperitenone reductase. We identified a rare catalytic residue substitution in the last two, and performed comparative crystal structure analyses and residue-swapping mutagenesis to investigate whether this determines the reaction outcome. The result was a complete loss of native activity and a switch between ene reduction and ketoreduction. This suggests the importance of a catalytic glutamate vs. tyrosine residue in determining the outcome of the reduction of α,β-unsaturated alkenes, due to the substrate occupying different binding conformations, and possibly also to the relative acidities of the two residues. This simple switch in mechanism by a single amino acid substitution could potentially generate a large number of de novo ene reductases.

PubMed: 27411040
DOI: 10.1002/anie.201603785

Experimental method

X-RAY DIFFRACTION (2.24 Å)