Gephyrin

Gephyrin is a multifunctional enzyme in all eukaryotes, catalyzes the two steps of the molybdenum cofactor biosynthesis. It acts also as a structural protein in animals in inhibitory post- synaptic. Mutations in the gene GPHN of people can lead to enzyme deficiency and so the rare hereditary disease molybdenum cofactor deficiency.

Catalyzed reactions

Overall, the following reaction is catalyzed, the intermediate step is not displayed:

ATP MoO42 -   AMP PPi Cu2

Molybdopterin (Cu) is reacted with molybdate to MoCo, ATP is consumed. The MoCo is desulfurized and may be used only by special enzymes.

Function in the cell structure

Analogous to the PSD -95 at excitatory synapses gephyrin is considered crucial element framework for the organization of the postsynaptic. Gephyrin was discovered by binding to glycine receptors that inhibit nerve cells, especially in the spinal cord and brain stem. However, it also binds directly to GABA receptors, the major inhibitory receptors in other central nervous system.

In cells Gephyrin is usually present as oligomer, the base appears to be a trimer conformation. Different splice variants of these prevent oligomerization, without affecting the binding to the receptors. Nevertheless, you disturb the composition of the inhibitory postsynaptic and may play a role in diseases such as epilepsy.

Thus, the gephyrin -level change significantly in some forms of experimentally induced epilepsy. Utter gephyrin deficiency results in an animal model to stiff muscles and death immediately after birth. Stiff muscles are also a symptom of hyperekplexia and Stiff - person syndrome, they are not sufficiently inhibited in both diseases. Cause may be a mutation in the gephyrin gene or the elimination of the protein by auto-antibodies.

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