home   genetic news   bioinformatics   biotechnology   literature   journals   ethics   positions   events   sitemap
 
  HUM-MOLGEN -> Genetic News | search  
 

Viral Spike Structure Provides a Foundation for Drug Design Against Paramyxoviruses

 
  November, 4 2000 3:37
your information resource in human molecular genetics
 
     
Newcastle disease is considered one of the most serious infectious diseases of birds, inflicting commercial and wild flocks alike. It is particularly devastating to chickens where the death rate can reach ~100%. Newcastle disease is caused by strains of a virus in the paramyxoviridae family; other members of this family cause human diseases such as mumps, as well as upper respiratory infections (for example, croup) in children. While vaccines are available to prevent infection of the Newcastle disease virus and some paramyxoviruses, there is currently no effective treatment against these pathogens after infection.

On the surface of these viruses are 'spikes' containing two proteins, one of which is called hemagglutinin-neuraminidase (HN). The spikes are the major components that elicit the immune response in the host organism; moreover, HN is essential for two steps in the viral infection cycle: host cell targeting and viral maturation. In the early step of infection, the HN protein targets the virus particle to the host cell: HN binds to a compound called sialic acid on the cell surface. In the maturation step, the newly formed virus buds from the host cell, and sialic acid compounds on the surface of the emerging viruses are removed by the HN protein, to prevent self-attachment of the virus particles. Inhibiting either function of HN disrupts the viral infection cycle. Thus, the HN protein is potentially a good target for developing treatments against this family of viruses.

To understand how the HN protein performs its functions, Garry Taylor of the University of St. Andrews, UK, and coworkers have determined the X-ray crystal structures of the catalytic domain of HN from the Newcastle disease virus in complex with either an enzyme inhibitor or a compound that resembles the substrate (Nature Structural Biology, 01 Nov 2000). These structures support a surprising hypothesis - that a single active site is utilized for both functions of the HN protein. In other words, both the stable binding of HN to sialic acid on the host cell surface during the targeting step and the removal (cleavage) of sialic acid from the viral surface during the maturation step appear to occur in the same place on the HN protein. Switching between these two functions is apparently regulated by conformational changes within the protein. These structures provide a foundation for structure-based drug design against the paramyxoviruses.

Contact information:

Dr. Garry Taylor
Centre for Biomolecular Sciences
University of St. Andrews
Fife, Scotland, KY16 9ST
United Kingdom

Telephone: 44 1334-467301
Fax: 44 1334-462595
E-mail: glt2@st-andrews.ac.uk

(C) Nature Structural Biology press release.


Message posted by: Trevor M. D'Souza

print this article mail this article
Bookmark and Share this page (what is this?)

Social bookmarking allows users to save and categorise a personal collection of bookmarks and share them with others. This is different to using your own browser bookmarks which are available using the menus within your web browser.

Use the links below to share this article on the social bookmarking site of your choice.

Read more about social bookmarking at Wikipedia - Social Bookmarking

Latest News
Variants Associated with Pediatric Allergic Disorder

Mutations in PHF6 Found in T-Cell Leukemia

Genetic Risk Variant for Urinary Bladder Cancer

Antibody Has Therapeutic Effect on Mice with ALS

Regulating P53 Activity in Cancer Cells

Anti-RNA Therapy Counters Breast Cancer Spread

Mitochondrial DNA Diversity

The Power of RNA Sequencing

‘Pro-Ageing' Therapy for Cancer?

Niche Genetics Influence Leukaemia

Molecular Biology: Clinical Promise for RNA Interference

Chemoprevention Cocktail for Colon Cancer

more news ...

Generated by News Editor 2.0 by Kai Garlipp
WWW: Kai Garlipp, Frank S. Zollmann.
7.0 © 1995-2016 HUM-MOLGEN. All rights reserved. Liability, Copyright and Imprint.