Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
PZ HTL SA

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

By BiotechDaily International staff writers
Posted on 21 Jan 2014
Image: Three-dimensional molecular space-fill model of tetrabenazine (TBZ) (Photo courtesy of Wikimedia Commons).
Image: Three-dimensional molecular space-fill model of tetrabenazine (TBZ) (Photo courtesy of Wikimedia Commons).
A mutagenesis study utilizing a human gene expressed by yeast cells has yielded new insights into the molecular mechanism controlling binding of neurotransmitters in the brain.

The study focused on the transport of monoamines into storage vesicles, which is mediated by vesicular monoamine transporter 2 (VMAT2) and is inhibited by the drug tetrabenazine (TBZ), which is used to control the jerky involuntary movements that occur in Huntington's disease and related disorders.

VMAT2, a member of the DHA12 family of multidrug transporters, is an integral membrane protein that transports monoamines—particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine—from the cellular cytosol into synaptic vesicles. 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.

Related Links:

Hebrew University of Jerusalem



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Disruption and removal of malaria parasites by the experimental drug (+)-SJ733 (Photo courtesy of the University of California, San Francisco).

Experimental Antimalaria Drug Induces the Immune System to Destroy Infected Red Blood Cells

An experimental drug for the treatment of malaria was found to induce morphological changes in infected erythrocytes that enabled the immune system to recognize and eliminate them. Investigators at... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Business

view channel

R&D Partnership Initiated to Reduce Development Time for New Drugs

nanoPET Pharma, GmbH (Berlin, Germany) signed an open-ended framework contract with the international pharmaceutical company Boehringer Ingelheim (Ridgefield, CT, USA). By developing customized contrast agents for research in both basic and preclinical studies, nanoPET Pharma will contribute to the enhancement of Boehringer... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.