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:6/24/2016)... ... ... Those who have experienced traumatic events may suffer from a complex set ... drug or alcohol abuse, as a coping mechanism. To avoid this pain and suffering, ... traumatic event. , Trauma sufferers tend to feel a range of emotions, from depression, ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... Conference and Scientific Sessions in Dallas that it will receive two significant new ... the grants came as PHA marked its 25th anniversary by recognizing patients, medical ...
(Date:6/24/2016)... ... 2016 , ... Comfort Keepers® of San Diego, CA is excited to announce ... program to drive cancer patients to and from their cancer treatments. Comfort Keepers ... of life and ongoing independence. Getting to and from medical treatments is one ...
(Date:6/24/2016)... ... June 24, 2016 , ... EB Medicine ... Making in Emergency Medicine conference in Ponte Vedra Beach, FL. The awards honor ... Emergency Medicine Practice and Pediatric Emergency Medicine Practice. , “With this ...
(Date:6/24/2016)... ... 2016 , ... Strategic Capital Partners, LLC (SCP) in concert ... capital for emerging technology companies. SCP has delivered investment events and professional ... than a million dollars of capital investment for five companies. The ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016 ... CAPR ), a biotechnology company focused on the ... announced that patient enrollment in its ongoing randomized ... has exceeded 50% of its 24-patient target. Capricor ... the third quarter of 2016, and to report ...
(Date:6/23/2016)... Pa. , June 23, 2016 Bracket ... will launch its next generation clinical outcomes platform, Bracket eCOA ... Meeting held on June 26 – 30, 2016 in ... the first electronic Clinical Outcome Assessment product of its kind ... Booth #715. Bracket eCOA 6.0 is a flexible ...
(Date:6/23/2016)... INDIANAPOLIS , June 23, 2016 /PRNewswire/ ... Diabetes Tomorrow,s Leaders Scholarship is any indication, the future ... today online at www.diabetesscholars.org by the Diabetes ... stand in the way of academic and community service ... scholarship program since 2012, and continues to advocate for ...
Breaking Medicine Technology: