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Alcohol Dehydrogenase D From Pyrococcus furiosus is a Thermostable Rare Earth Element Binding Enzyme: Metal/cofactor
Ipek Simay Gokulu1, Sameera Abeyrathna1, Scott Banta1
1Department of Chemical Engineering, Columbia University, New York, NY 10027, USA.
Journal of Molecular Biology
|July 24, 2026
Summary
Rare earth elements (REEs) can bind to alcohol dehydrogenase D (AdhD), accelerating its forward reaction while inhibiting the reverse. This cofactor-dependent binding mechanism influences enzyme catalysis and directionality.
Area of Science:
- Biochemistry
- Enzymology
- Bioinorganic Chemistry
Background:
- Metals are common in enzyme active sites, but rare earth elements (REEs) are less explored in biocatalysis.
- Alcohol dehydrogenase D (AdhD) and human aldose reductase (hAR) belong to the aldo-keto reductase (AKR) family.
Purpose of the Study:
- To investigate the interaction of REEs with AdhD and their impact on enzymatic activity.
- To elucidate the mechanism of REE-dependent modulation of catalysis in AKR family enzymes.
Main Methods:
- Structural analysis to identify REE binding sites.
- Enzyme kinetics assays to measure catalytic activity and equilibrium constants.
- Cofactor binding studies under varying redox states.
Main Results:
- AdhD binds REE ions, with a second binding site identified in the presence of cofactor.
- REEs accelerate the forward (oxidation) and inhibit the reverse reaction of AdhD.
- REE binding is cofactor redox-state dependent and attenuates enzyme-cofactor complex formation.
- Similar REE-dependent modulation was observed in human aldose reductase (hAR).
Conclusions:
- REEs tune enzyme catalytic directionality and apparent thermodynamics via cofactor-dependent binding.
- This mechanism involves linkage effects rather than direct active-site metal catalysis.
- A conserved REE interaction mechanism is suggested for the AKR enzyme family.
Keywords:
cofactor-dependent metal bindingenzyme kineticslanthanide-dependent catalysisreaction equilibriumMore Related Videos
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