Dual Pathways for Water Activation in IMP Dehydrogenase
Author Information
Author(s): Min Donghong, Josephine Helen R, Li Hongzhi, Lakner Clemens, MacPherson Iain S, Naylor Gavin J. P, Swofford David, Hedstrom Lizbeth, Yang Wei
Primary Institution: Florida State University
Hypothesis
How did Nature construct such a complicated catalyst?
Conclusion
The study reveals that IMP dehydrogenase has two pathways for activating water, one of which may represent an evolutionary remnant.
Supporting Evidence
- The simulations showed that the lowest energy pathway for water activation involves Arg418.
- A second pathway for water activation was identified, involving Thr321 and Glu431.
- Experimental validation confirmed the predictions made by the simulations regarding the pH-rate profile.
Takeaway
Scientists found that an enzyme called IMP dehydrogenase can use two different methods to activate water, which helps it do its job. One of these methods is very old and might have been used by early versions of the enzyme.
Methodology
The study used hybrid quantum mechanical/molecular mechanical simulations to investigate the mechanisms of water activation in IMP dehydrogenase.
Digital Object Identifier (DOI)
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