Navigation Links
Oxidation defense in mosquitoes benefits malaria parasite

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 transf orming 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.


'"/>

Source:Virginia Tech


Related biology news :

1. Female sex hormones play a vital role in defense against sexually transmitted diseases
2. In the sea slugs defense against lobsters, confusion is key
3. Disease diagnosis, biodefense among UH chemical research projects
4. Comprehensive biodefense text published
5. Ancient immune defense mechanism is no match for HIV-1
6. Discovery could be key to bioterrorism defense
7. Variation in HIVs ability to disable host defenses contributes to rapid evolution
8. Scientists show that tick-borne flaviviruses use a novel mechanism to evade host defenses
9. Researchers uncover E. colis defense mechanism
10. Energy management in cells may hold key to cancer defense
11. Bacteria recognize antimicrobials, respond with counter-defenses
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/8/2016)... , February 8, 2016 ... payment platform which presents innovation for clients, comfort ... feature called VoiceKey. --> Worldcore ... presents innovation for clients, comfort and unbeatable security, ... --> Worldcore is the ...
(Date:2/3/2016)... Vigilant Solutions announces today that the ... Missouri solved two recent hit-and-run cases with ... Vigilant Solutions. Brian Wenberg explains, "I ... was walking out of a convenience store and witnessed an elderly male back ... striking his vehicle and leaving the scene.  In his ...
(Date:2/2/2016)... 2, 2016 Technology Enhancements Accelerate Growth of X-ray ... the digital and computed radiography markets in ... Indonesia (TIM). It provides an ... as well as regional market drivers and restraints. The ... penetration and market attractiveness, both for digital and computed ...
Breaking Biology News(10 mins):
(Date:2/12/2016)... ... February 12, 2016 , ... The Pittcon 2016 Exposition, ... Georgia, will include 848 exhibitors (count as of February 9) of which 119 ... services used by the scientific community in industrial, academic, and government labs. The ...
(Date:2/11/2016)... DIEGO, Feb. 11, 2016  Neurocrine Biosciences, Inc. (NASDAQ: NBIX ... ended December 31, 2015. --> ... a net loss of $29.3 million, or $0.34 loss per share, ... per share for the same period in 2014. For the year ... $88.9 million, or $1.05 loss per share, as compared to a ...
(Date:2/11/2016)... ATLANTA , Feb. 11, 2016  Wellcentive ... a Portland, Oregon -based community ... to provide population health analytics, quality reporting and ... help FamilyCare strengthen its team of quality managers, ... reporting to the provider groups serving FamilyCare members. ...
(Date:2/11/2016)... ... February 11, 2016 , ... Reichert ... years, continues today to pursue the highest level of accuracy and quality with ... AR9 Refractometer and the AR5 Refractometer. Accurate, reliable and tough enough for ...
Breaking Biology Technology: