Spontaneous oxidation of 3-hydroxykynureine (3-HK), a metabolic intermediate of the tryptophan degradation pathway, elicits a remarkable oxidative stress response in animal tissues. In the yellow fever mosquito Aedes aegypti the excess of this toxic metabolic intermediate is efficiently removed by a specific 3-HK transaminase, which converts 3-HK into the more stable compound xanthurenic acid. In anopheline mosquitoes transmitting malaria, xanthurenic acid plays an important role in Plasmodium gametocyte maturation and fertility. Using the sequence information provided by the Anopheles gambiae genome and available ESTs, we adopted a PCR-based approach to isolate a 3-HK transaminase coding sequence from the main human malaria vector A. gambiae. Tissue and developmental expression analysis revealed an almost ubiquitary profile, which is in agreement with the physiological role of the enzyme in mosquito development and 3-HK detoxification. A high yield procedure for the expression and purification of a fully active recombinant version of the protein has been developed. Recombinant A. gambiae 3-HK transaminase is a dimeric pyridoxal 5′-phosphate dependent enzyme, showing an optimum pH of 7.8 and a comparable catalytic efficiency for both 3-HK and its immediate catabolic precursor kynurenine. This study may be useful for the identification of 3-HK transaminase inhibitors of potential interest as malaria transmission-blocking drugs or effective insecticides.

Identification and biochemical characterization of the Anopheles gambiae 3-hydroxykynurenine transaminase / F., Rossi; Lombardo, Fabrizio; A., Paglino; C., Cassani; G., Miglio; Arca', Bruno; M., Rizzi. - In: THE FEBS JOURNAL. - ISSN 1742-464X. - STAMPA. - 272:(2005), pp. 5653-5662. [10.1111/j.1742-4658.2005.04961.x]

Identification and biochemical characterization of the Anopheles gambiae 3-hydroxykynurenine transaminase.

LOMBARDO, Fabrizio;ARCA', Bruno;
2005

Abstract

Spontaneous oxidation of 3-hydroxykynureine (3-HK), a metabolic intermediate of the tryptophan degradation pathway, elicits a remarkable oxidative stress response in animal tissues. In the yellow fever mosquito Aedes aegypti the excess of this toxic metabolic intermediate is efficiently removed by a specific 3-HK transaminase, which converts 3-HK into the more stable compound xanthurenic acid. In anopheline mosquitoes transmitting malaria, xanthurenic acid plays an important role in Plasmodium gametocyte maturation and fertility. Using the sequence information provided by the Anopheles gambiae genome and available ESTs, we adopted a PCR-based approach to isolate a 3-HK transaminase coding sequence from the main human malaria vector A. gambiae. Tissue and developmental expression analysis revealed an almost ubiquitary profile, which is in agreement with the physiological role of the enzyme in mosquito development and 3-HK detoxification. A high yield procedure for the expression and purification of a fully active recombinant version of the protein has been developed. Recombinant A. gambiae 3-HK transaminase is a dimeric pyridoxal 5′-phosphate dependent enzyme, showing an optimum pH of 7.8 and a comparable catalytic efficiency for both 3-HK and its immediate catabolic precursor kynurenine. This study may be useful for the identification of 3-HK transaminase inhibitors of potential interest as malaria transmission-blocking drugs or effective insecticides.
2005
Anopheles gambiae; 3 hydroxykynurenine transaminase; xanthurenic acid; Plasmodium gametogenesis; PLP dependent enzyme
01 Pubblicazione su rivista::01a Articolo in rivista
Identification and biochemical characterization of the Anopheles gambiae 3-hydroxykynurenine transaminase / F., Rossi; Lombardo, Fabrizio; A., Paglino; C., Cassani; G., Miglio; Arca', Bruno; M., Rizzi. - In: THE FEBS JOURNAL. - ISSN 1742-464X. - STAMPA. - 272:(2005), pp. 5653-5662. [10.1111/j.1742-4658.2005.04961.x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/439742
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