Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Oxidation defense in mosquitoes benefits malaria parasite

04.04.2006
Scientists discover structure of defense process, how to inhibit it

Scientists from two universities in Italy and Virginia Tech in the United States have determined the structure of a protein that is responsible for the production xanthurenic acid (XA) in Anopheles gambiae, the malaria carrying mosquitoes. XA plays a key role in the sexual reproduction of the malaria parasite (Plasmodium falciparum) in A. gambiae mosquitoes. Interfering with the formation of XA could be an avenue for development of drugs and insecticides to block malaria transmission. Millions of people worldwide are infected with malaria.

The research will be presented in the Proceedings of the National Academy of Science (PNAS) on-line as early as April 3 and in print April 11, 2006 ("Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase" by Franca Rossi, Silvia Garavaglia, and Giovanni Battista Giovenzana, of the DiSCAFF-Drug and Food Biotechnology Center at the University of Piemonte Orientale ’Amedeo Avogadro’; Bruno Arca’ of the Department of Biological Structure and Function at the University of Napoli ’Federico II’; Jianyong Li of the Department of Biochemistry at Virginia Tech, and Menico Rizzi, also of the University of Piemonte Orientale).

The synthesis of XA is one of the biochemical defenses against oxidative stress resulting from 3-hydroxykynurenine (3-HK) accumulation in mosquitoes and possibly other species as well. "3-HK is oxidized easily under physiological condition, stimulating the production of reactive oxygen species, which can damage cells," said Li.

Mammals have various biochemical pathways of disposing of 3-HK, which mosquitoes lack. Research by Li’s group at Virginia Tech on Aedes aegypti mosquitoes determined that "mosquitoes have developed an efficient strategy to prevent the accumulation of 3-HK by converting the chemically reactive 3-HK to the chemically stable XA via transaminase-mediated reactions," said Li.

The protein described in the PNAS article is responsible for this transforming of 3-HK into XA in the malaria vector Anopheles gambiae, where XA also helps the malarial parasite reproduce. So stopping the oxidative defense could stop the parasite as well as make the insect a victim of oxidative stress.

Rizzi’s group at the University of Piemonte Orientale focuses on the structural characterization of enzymes involved in tryptophan degradation in mosquitoes, which results in the synthesis of XA. "Deciphering the molecular architecture of each enzyme in this pathway will be used for the structure-based rational design of potent and highly selective inhibitors of potential interest as innovative antimalarial agents," said Rizzi

Li’s group at Virginia Tech biochemically characterizes enzymes involved in conversion to XA, including trptophan, the initial precursor of the process.

The researchers have collaborated since 2003.

"The use of protein crystallography in combination with biochemical studies and medicinal chemistry, represents a highly multidisciplinary approach that could lead to the identification of novel agents for the treatment of malaria," said Rizzi.

The PNAS article describes what an International team of scientists learned about the structure of Anopheles gambiae 3-HK transaminase. The research will continue on the rational design of a small molecule that could be synthesized, and that would allow the malaria cycle to be interrupted, therefore representing a novel avenue for the treatment of malaria.

Susan Trulove | EurekAlert!
Further information:
http://www.vt.edu

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>