Featured Research

from universities, journals, and other organizations

Enzymes possible targets for new anti-malaria drugs

Date:
September 27, 2011
Source:
Virginia Tech
Summary:
Researchers have validated that two enzymes used by malaria parasites to chew up human hemoglobin are potential anti-malarial drug targets.

Researchers at the Perelman School of Medicine at the University of Pennsylvania, Monash University, and Virginia Tech have used a set of novel inhibitors to analyze how the malaria parasite, Plasmodium falciparum, uses enzymes to chew up human hemoglobin from host red blood cells as a food source. They have validated that two of these parasite enzymes called peptidases are potential anti-malarial drug targets.

The research appeared in the Aug. 15 early online issue of the Proceedings of the National Academy Sciences.

"The basis for this research was to use small molecule inhibitors to help understand the biology of the malaria parasite and to find new drug targets as drug-resistant parasites necessitate the discovery of new antimalarials," said Doron C. Greenbaum, assistant professor of pharmacology at Penn, who lead the collaborative study.

The P. falciparum parasite, delivered in a mosquito bite, causes malaria once it takes up residence in the human host's red blood cells and begins to digest hemoglobin, the protein that carries oxygen. The parasite multiplies and is picked up from the bloodstream when the mosquito feeds. Scientists are interested in determining which enzymes are responsible for generating amino acids from the hemoglobin in the feeding process.

Two enzymes, called aminopeptidases, have been proposed as being responsible for releasing single amino acids from proteins, or peptides. However, "there has been controversy regarding where this takes place and which enzymes are responsible," said Michael Klemba, associate professor of biochemistry with the Vector-Borne Infectious Disease Research Group at Virginia Tech, who collaborated on the evaluation of new aminopeptidase inhibitors with Greenbaum's lab. "It has been difficult to study their specific roles in breaking down hemoglobin."

The Penn team developed chemical genetic tools called activity-based probes that enabled the researchers to specifically inhibit one or the other of the enzymes. "When we inhibited the parasite enzyme PfA-M1, it blocked hemoglobin degradation, starving the parasite to death," said Greenbaum.

Inhibition of a second enzyme, leucyl aminopeptidase, showed it to have an important role, but earlier in the parasite's life cycle within the red blood cell.

"Our collective data suggest that these two MAPs are both potential antiparasitic drug targets," said Greenbaum.

Other co-authors on the paper are Geetha Velmourougane, postdoctoral fellow at Penn; Seema Dalal, research scientist in biochemistry at Virginia Tech; Gilana Reiss, graduate student in Pharmacology, Penn; James C. Whisstock, Monash University, Logan Fellow and scientific director of the Victorian Bioinformatics Consortium; Ozlem Onder, postdoctoral associate in biology, and Dustin Brisson, assistant professor of biology, both at Penn; Sheena McGowan, senior research fellow at Monash University.

"Dr. Greenbaum's team developed the probes and Virginia Tech's researchers tested the probes on purified enzymes and determined the potency of the probes against each of the two aminopeptidases," said Klemba. "Dr. Whisstock's team at Monash University did the structural biology, providing the high-resolution atomic structure of the enzymes."


Story Source:

The above story is based on materials provided by Virginia Tech. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. B. Harbut, G. Velmourougane, S. Dalal, G. Reiss, J. C. Whisstock, O. Onder, D. Brisson, S. McGowan, M. Klemba, D. C. Greenbaum. PNAS Plus: Bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases. Proceedings of the National Academy of Sciences, 2011; 108 (34): E526 DOI: 10.1073/pnas.1105601108

Cite This Page:

Virginia Tech. "Enzymes possible targets for new anti-malaria drugs." ScienceDaily. ScienceDaily, 27 September 2011. <www.sciencedaily.com/releases/2011/09/110927112417.htm>.
Virginia Tech. (2011, September 27). Enzymes possible targets for new anti-malaria drugs. ScienceDaily. Retrieved April 16, 2014 from www.sciencedaily.com/releases/2011/09/110927112417.htm
Virginia Tech. "Enzymes possible targets for new anti-malaria drugs." ScienceDaily. www.sciencedaily.com/releases/2011/09/110927112417.htm (accessed April 16, 2014).

Share This



More Health & Medicine News

Wednesday, April 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Formerly Conjoined Twins Released From Dallas Hospital

Formerly Conjoined Twins Released From Dallas Hospital

Newsy (Apr. 16, 2014) Conjoined twins Emmett and Owen Ezell were separated by doctors in August. Now, nearly nine months later, they're being released from the hospital. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com
Cognitive Function: Is It All Downhill From Age 24?

Cognitive Function: Is It All Downhill From Age 24?

Newsy (Apr. 15, 2014) A new study out of Canada says cognitive motor performance begins deteriorating around age 24. Video provided by Newsy
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