( Scientists from two universities in Ita...)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
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Source:Virginia Tech

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