Fluoride reactivates D165S glutamate dehydrogenase.

What is it about?

The crystal structure of GDH identified for the first time a catalytic Asp residue, D165. Its role was tested by mutagenesis and the mutant D165S was virtually inactive. However, a chance observation led us to the disocovery that fluoride, which inhibits the wild-type enzyme, dramatically (1000-fold) enhances the feeble residual activiuty of D165N. The net result is that whereas, without fluoride there is a 100,000 fold difference in activity between wild type and D165N, with 1M fluoride this collapses to a 5-fold difference! The effect is highly specific to the small F- ion.

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Why is it important?

This dramatic finding raises questions about exactly how D165 acts in normal catalysis and how the fluoride ion is able to bring about chemical rescue.