Featured Research

from universities, journals, and other organizations

Creating Less Toxic Anti-HIV Drugs: Discovery Of Enzyme Structure Points The Way

Date:
October 16, 2009
Source:
University of Texas at Austin
Summary:
By discovering the atomic structure of a key human enzyme, researchers have pointed the way toward designing anti-HIV drugs with far less toxic side effects.

By discovering the atomic structure of a key human enzyme, researchers at The University of Texas at Austin have pointed the way toward designing anti-HIV drugs with far less toxic side effects.

Their work was published this week in Cell.

"Many anti-HIV drugs are designed to stop the process of DNA replication," says Dr. Whitney Yin, assistant professor of chemistry and biochemistry. "That turns out to be a great thing to do to help cure virus infections, because it stop the processes of viral replication.

"At the same time, however, when you target such a critical process in viruses, you may also target human enzymes that perform similar functions in normal cells, and this is what causes harmful drug side effects."

Yin and her graduate student, Young-sam Lee, have solved the atomic structure of an enzyme, known as Pol γ (pol gamma), that is responsible for DNA replication in human mitochondria.

When mitochondria are working normally, they produce most of the energy that sustains human cells. When pol gamma comes into contact with certain anti-retroviral drugs, however, it can incorporate the drug into mitochondrial DNA, and thus interfere with the normal replication process. This interferes with the ability of mitochondria to function. The consequences can range from simple nausea to bone marrow depletion to organ failure.

"Patients who are taking this class of anti-HIV drugs have suffered these drug toxicities for a long time," says Yin. "Dosages and combinations of drugs can be chosen so they don't kill you, but they still can't be used at their most effective concentrations against HIV. However, in large part because combination therapies have become more successful and patients are living longer, toxicity has become more of an issue than before."

Although it's been known for some time that pol gamma is responsible for mediating the toxicity of the drugs, Yin says, it has been difficult to design a drug that can distinguish between HIV and pol gamma without knowing the structure of pol gamma. With the structures of both pol gamma and HIV known, the differences between the two can be exploited in the design of new drugs that will be more selective (and thus less toxic) against HIV.

"This is a unique opportunity for drug design," says Yin. "Now you have two pictures side by side. You have the viral target protein and the human protein. You know not to do anything in this region where the two proteins are similar, but rather focus in areas where they're different."

In addition to its relevance to anti-HIV drug design, Yin's research is also helping to explain how mutations in pol gamma lead to various degenerative diseases, including epilepsy, encephalopathy and Alpers' syndrome (a fatal childhood disease leading to brain and liver failure).

The National Institutes of Health (NIH) and the Welch Foundation funded the work.


Story Source:

The above story is based on materials provided by University of Texas at Austin. Note: Materials may be edited for content and length.


Cite This Page:

University of Texas at Austin. "Creating Less Toxic Anti-HIV Drugs: Discovery Of Enzyme Structure Points The Way." ScienceDaily. ScienceDaily, 16 October 2009. <www.sciencedaily.com/releases/2009/10/091015123555.htm>.
University of Texas at Austin. (2009, October 16). Creating Less Toxic Anti-HIV Drugs: Discovery Of Enzyme Structure Points The Way. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2009/10/091015123555.htm
University of Texas at Austin. "Creating Less Toxic Anti-HIV Drugs: Discovery Of Enzyme Structure Points The Way." ScienceDaily. www.sciencedaily.com/releases/2009/10/091015123555.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins