Navigation Links
Structure of DNA-modifying enzyme In Small Pox Determined

Researchers have determined the structure of DNA-modifying enzyme that could help fight the smallpox disease better. In a study published in the August 4 issue of Molecular Cell//, the researchers at the University of Pennsylvania School of Medicine have presented their findings on the structure of topoisomerase enzyme and how it binds to DNA. The findings could help in developing antiviral agents more effective in fighting the disease.

"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 stru cture 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 p articles.

Source: Eurkalert
'"/>




Related medicine news :

1. Relationship Between Genetic Structure And Quality of Life
2. Abnormal Brain Structure One Of The Reasons For Depression in Adolescents
3. Structure of the brain to increase risk for anxiety disorders
4. Changes In Brain Structure From Methamphetamine Abuse And HIV Infection
5. Almond Structure in the Brain Intrigues Researchers
6. Controversy over Fees Structure in Private Medical Colleges
7. Controversy Over The Fee Structure In Private Medical Colleges Surfaces Yet Again
8. Education Structure In Indian Schools To Be Revamped Soon
9. Neither Management Nor Students Happy With New Fee Structure
10. DNA-bound p53 Tumor Suppressor Protein Structure Determined
11. Penn Researchers Throw Light on the Structure Of Smallpox Virus Protein
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/29/2016)... ... , ... Coast Dental Fort Stewart is celebrating its grand opening with an ... Furniture Mall at 112 Vilseck Road in Fort Stewart. There will be refreshments, giveaways, ... have the opportunity to meet general dentists Thomas Richards, DDS, and Josh Faulk, DMD, ...
(Date:4/29/2016)... ... ... Spine Team Texas, a comprehensive spine physician group specializing in the treatment of ... invited to be a featured speaker at the Texas Society of the American College ... , Dr. R. Scott McPherson, a physical medicine and rehabilitation specialist, will speak ...
(Date:4/29/2016)... ... April 29, 2016 , ... Mobility Designed is redefining mobility ... the armpits, the M+D Crutch evenly distributes body weight from the elbow to the ... when using the crutches than with other crutches. , Co-founders Max and Liliana Younger ...
(Date:4/29/2016)... ... April 29, 2016 , ... The ... (CCA), is pleased to announce the launch of the GFCP Scoop ... and more. The purpose of the GFCP Scoop site is to ...
(Date:4/29/2016)... ... 29, 2016 , ... Dr. Robert Mondavi, one of the dentists in ... is a fast-growing field as more patients are discovering the many different ways they ... the options currently available to them and which ones might work for their smiles. ...
Breaking Medicine News(10 mins):
(Date:4/29/2016)... , April 29, 2016 ... Review, H1 2016" market research report that provides ... with comparative analysis at various stages, therapeutics assessment ... of administration (RoA) and molecule type, along with ... It also reviews key players involved in the ...
(Date:4/29/2016)... , April 29, 2016 ... life science laboratory due to the growing demands for ... advance technology, contemporary automated systems are already adept of ... by slow, tedious and manual labor. Instrumentation continues to ... not even conceivable just a few years ago. Originally ...
(Date:4/28/2016)... April 28, 2016  Marking its one year ... and ovarian cancer risk test, Color Genomics ... genes that highly impact the most common hereditary ... the Color Test analyzes hereditary cancer risks for ... uterine cancers. The Color Test is physician ordered ...
Breaking Medicine Technology: