Results of Mutagenesis Study Expected to Guide Development of Drugs for Nervous System Disorders

Irregularities in storage and transport of these neurotransmitters causes brain disorders and nervous system diseases, including Huntington's disease, Parkinson's disease, and various motor dysfunctions.

Investigators at the Hebrew University of Jerusalem (Israel) studied the interaction between VMAT2 and TBZ by implanting the human VMAT2 gene into yeast cells and then screening for mutants that were resistant to TBZ inhibition.

They reported in the November 8, 2013, issue of the Journal of Biological Chemistry that at the molecular level TBZ mapped to either conserved proline or glycine resdues, or to residues immediately adjacent to conserved proline and glycine. The data strongly suggested that these conserved alpha-helix breaking residues played an important role in conformational rearrangements required for TBZ binding and substrate transport.

These results provide a novel insight into the mechanism of neurotransmitter transport and TBZ binding by VMAT2, which is expected to aid in the formulation of new drug designs.

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Hebrew University of Jerusalem