Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

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

By BiotechDaily International staff writers
Posted on 21 Jan 2014
Print article
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



Print article

Channels

Drug Discovery

view channel
Image: Naturally occurring clay from Kisameet Bay, Canada, exhibits potent antibacterial activity against multidrug-resistant pathogens (Photo courtesy of Kisameet Glacial Clay Inc.).

Antibiotic Resistant Bacteria Succumb to Treatment with Unique Natural Clay

A team of Canadian medical microbiologists has demonstrated the potential use of a unique type of natural clay for treating pathogenic bacteria that have become resistant to the commonly used antibiotics.... Read more

Business

view channel

Purchase Agreement to Boost Ebola Vaccine Development

A deal to help boost development of a vaccine to protect against Ebolavirus infection was finalized at the recent Davos Conference in Switzerland. Gavi (Geneva, Switzerland), the global alliance for vaccines and immunizations, announced that it would spend five million USD to purchase the Ebola vaccine under development... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.