Navigation Links
Penn Researchers Throw Light on the Structure Of Smallpox Virus Protein

Researchers at the University of Pennsylvania School of Medicine have shown the form of a crucial smallpox virus and the manner with which it attaches// itself to the DNA .The enzyme, which is named, as a topoisomerase has become a very important drug target for devising novel methods to combat small pox.

"This enzyme is one of the most closely studied DNA-modifying enzymes in biology," says Frederic D. Bushman, PhD, Professor of Microbiology, one of the senior authors. "The structure of the DNA complex has been long-awaited." DNA-modifying enzymes bind to specific sequences in the genetic code to aid in the many steps of DNA replication.

The smallpox virus is one of the most easily transmissible infectious diseases known to humans, resulting in up to 30 percent mortality. The efficiency with which it spreads, combined with the deadly nature of the disease, has raised fears that smallpox could be revived for use in bioterrorism. Knowing the exact three-dimensional structure of smallpox virus proteins could help researchers design antiviral agents, but few structures of whole viral proteins exist.

Poxviruses are large viruses that contain two strands of DNA and replicate themselves entirely in the cytoplasm of infected cells. Poxviruses do not take over the genetic machinery inside the nucleus of the host cell, as many viruses do. Because of this strategy, poxviruses encode many of the enzymes they need to replicate their own genes, and hence reproduce. One of these enzymes is a topoisomerase, which is used by the virus to relieve the excessive twisting of DNA strands that normally occurs during DNA replication and transcription of the viral genes. Upon initial infection, the poxviruses come already equipped with some proteins, including topoisomerases, to kick-start replication.

The structure was determined in a collaborative effort between the Bushman lab and the lab of the other senior author Gregory D. Van Duyne, PhD, Professor of Biochemistry and Biophysics and an Investigator with the Howard Hughes Medical Institute (HHMI). Using purified topoisomerase enzyme that had been expressed in bacterial cells, they bound the enzyme to short segments of DNA that contained the viral topoisomerase's specific recognition sequence. They then determined the three-dimensional structure of the topoisomerase-DNA complex using X-ray crystallography.

One of the primary differences between the viral topoisomerase enzyme and the closely related human enzyme that functions in the nucleus of all human cells is that the viral enzyme only relaxes supercoiled DNA when it binds to specific DNA sequences. The structure of the poxvirus topoisomerase-DNA complex provides some important clues about how this recognition and activation mechanism works.

"The more the viral enzyme differs from the human nuclear enzyme, the more likely it is that inhibitors could be developed that are specific to the viral enzymes," says Bushman.

Knowing the three-dimensional structure of the smallpox virus topoisomerase-DNA complex will also facilitate the design of agents to combat poxvirus infections. Topoisomerases are some of the most widely targeted proteins by drugs that are intended to inhibit growth of the cell. Drugs that target topoisomerases generally stabilize an intermediate of the enzyme's reaction in which one of the DNA strands is broken. If these breaks are not repaired, the DNA cannot be replicated and the cell dies.

In the case of smallpox virus, the hope is that drugs targeted to the viral topoisomerase enzyme will prevent viral replication through a similar mechanism. The X-ray structure provides a template for designing small molecules that could stabilize the broken DNA in the intermediate form, thereby killing smallpox virus particles.

(Source: EurekaAlert)
'"/>




Related medicine news :

1. Researchers urge caution in using ear tube surgery
2. Researchers Scale to assess the Severity of Epilepsy in Kids
3. Researchers trick Alzheimers Enzyme
4. Researchers find new HIV hiding place
5. New Hair in 15 Days Could Now Be A Possibility Say Researchers
6. Researchers developed world’s smallest toothbrus
7. Researchers discover receptor cells that can cause epilepsy
8. 15 Anti-SARS Drugs Identified By China-Europe Team of Researchers
9. Researchers reversed the process of memory loss
10. Researchers Identify Key Gene That May Help Brain Treatment
11. Researchers Discover Protein That Causes Malaria
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:12/8/2016)... ... December 08, 2016 , ... ... (WCRI) officially opened registration today for its 33rd Annual Issues & Research ... . , The theme of the conference is “Persistent Challenges and New Opportunities: ...
(Date:12/8/2016)... ... 08, 2016 , ... CURE Media Group, the nation’s leading digital and print ... Upstage Lung Cancer in efforts to combat lung cancer, announced CURE Media Group President ... “CURE Media Group is honored to team up with Upstage Lung Cancer in order ...
(Date:12/8/2016)... (PRWEB) , ... December 08, ... ... Presence Suite 10.2 version gives development continuity to its innovative Unified Instance ... channels management capacity. In addition, this new version optimizes the unattended auto-dialing ...
(Date:12/8/2016)... , ... December 08, 2016 , ... ... after surgery as possible. With this in mind, SIGVARIS has created a new ... blood clot) during bed rest and provide the benefits of graduated compression when ...
(Date:12/8/2016)... ... December 08, 2016 , ... The ... offices headquartered in Jefferson County, is announcing the launch of a charity drive ... The number of homeless women and children in Birmingham has grown steadily since ...
Breaking Medicine News(10 mins):
(Date:12/9/2016)... -- Research and Markets has announced the addition ... report to their offering. ... Market growth can be attributed ... pharmaceutical and biotechnology industry and technological advancements like automation and ... and growing research activities in toxicology and stem cells provide ...
(Date:12/9/2016)... Research and Markets has announced the addition of the ... ... travel vaccines market to grow at a CAGR of 6.83% during ... and the growth prospects of the global travel vaccines market for ... generated from the sales of various vaccines administered to actively immunize ...
(Date:12/8/2016)... Dec. 8, 2016 Australia Ophthalmic Lasers Market ... "Australia Ophthalmic Lasers Market Outlook to 2022", provides key ... report provides value, in millions of US dollars, volume ... - Excimer Lasers, Femtosecond Lasers and YAG Lasers. ... data for each of these market segements, and global ...
Breaking Medicine Technology: