Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
GLOBETECH PUBLISHING
JIB

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: S-649266 has more robust antibacterial activity than established antibiotics against multidrug-resistant bacteria (Photo courtesy of Shionogi).

Novel Antibiotic Shows Potential for Broad Range of Infections

The emergence of bacterial resistance to known antibacterial agents is becoming a major challenge in treating the infection caused by multi drug resistant (MDR) bacteria. In order to treat bacterial... Read more

Lab Technologies

view channel
Image: Leica Microsystems launches the inverted research microscope platform Leica DMi8 (Photo courtesy of Leica Microsystems).

New Inverted Microscope Designed to Readily Adapt to Changing Research Demands

A new inverted microscope for biotech and other life science laboratories was designed to readily accommodate modifications and upgrades to allow it to keep current with changing research demands and interests.... Read more

Business

view channel

Collaboration of Mayo Clinic and IBM Cognitive Computer Devised to Improve Clinical Trial Research

The Mayo Clinic (Rochester, MN, USA) and IBM (Armonk, NY, USA) recently announced plans to pilot Watson, the IBM cognitive computer, to match patients more rapidly with suitable clinical trials. A proof-of-concept phase is currently ongoing, with the intent to introduce it into clinical use in early 2015.... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.