Semiempirical QM/MM calculations reveal a step-wise proton transfer and an unusual thiolate pocket in the mechanism of the unique arylpropionate racemase AMDase G74C

The mechanism of the unique arylpropionate racemase AMDase G74C was investigated by a QM/MM approach. Molecular dynamics simulations showed that the mechanism is initiated by a deprotonation of the catalytic cysteine. The simulations revealed two thiolate pockets. While the first plays a role in the...

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Bibliographic Details
Published in:Catalysis science & technology 2016-01, Vol.6 (13), p.4937-4944
Main Authors: Busch, F, Enoki, J, Hülsemann, N, Miyamoto, K, Bocola, M, Kourist, R
Format: Article
Language:English
Subjects:
Catalysis
Catalysts
Cysteine
Mathematical analysis
Molecular dynamics
Pocket
Racemization
Simulation
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Summary:The mechanism of the unique arylpropionate racemase AMDase G74C was investigated by a QM/MM approach. Molecular dynamics simulations showed that the mechanism is initiated by a deprotonation of the catalytic cysteine. The simulations revealed two thiolate pockets. While the first plays a role in the natural decarboxylative activity of AMDase, the second stabilizes the artificially introduced thiolate group of C74. The presence of the two structural motifs is a prerequisite for the promiscuous racemization reaction of AMDase G74C. QM/MM simulations show that the deprotonation and reprotonation proceed in a stepwise fashion, in which a planar enedionate intermediate is stabilized by a delocalized π-electron system on a vinylic or aromatic substituent of the substrate. The artificial racemase is thus a typical case of substrate-assisted catalysis. Semiempirical calculations on the mechanism of the arylpropionate racemase AMDase G74C reveal a step-wise mechanism involving a planar-enedionate intermediate.
ISSN:2044-4753
2044-4761
DOI:10.1039/c5cy01964h