Cel Plasmodium falciparum causes severe malaria and about 2 million human deaths annually. The main obstacle to combat the disease is increasing resistance of the parasites to existing drugs and the lack of a protective vaccine. Therefore, it is imperative that new suitable drug targets in the parasite?s metabolism are identified, assessed and validated. The availability of the parasite's genome sequence offers an excellent tool to identify metabolic pathways potentially essential for parasite survival. Scrutinising the Plasmodium genomes revealed that they possess biosynthetic pathways for vitamins. Vitamins are organic compounds required in small amounts to ensure normal metabolic functions. Since they are not synthesized by humans, they need to be supplied via nutrients in trace amounts. The absence of vitamin biosynthesis in humans suggests that specific targeting of these parasite pathways with inhibitors is feasible and thus vitamin biosynthesis of Plasmodium might offer excellent potential for the development of novel chemotherapeutics against malaria with specific toxicity towards the parasites without affecting the host's metabolism. In the first instance we will focus on vitamin B6 biosynthesis, as this important nutrient is required as a co-factor for a wide variety of essential metabolic functions in protein and amino acid metabolism and also has been implicated in the defence against oxidative stress in other eukaryotes. Using reverse genetic approaches we will validate the suitability of two of the vitamin B6 synthesising enzymes Pdx1 and Pdx2 respectively, as drug targets. In addition, their precise biological functions and potential interactions with other cellular components will be analyzed. Further the biochemical, biophysical and structural features of both enzymes will be assessed in order to be able to rationally design specific inhibitors that interfere with the parasite's proteins activities and functions. Dziedzina nauki medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health scienceshealth sciencesinfectious diseasesmalariamedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health sciencesbasic medicinephysiologyhomeostasisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Słowa kluczowe Malaria Plasmodium falciparum novel drug target vitamin B6 vitamin biosynthesis Program(-y) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Temat(-y) LIFESCIHEALTH-2.3.0 - Developing new promising candidate vaccines and therapies Zaproszenie do składania wniosków FP6-2003-LIFESCIHEALTH-3 Zobacz inne projekty w ramach tego zaproszenia System finansowania STREP - Specific Targeted Research Project Koordynator UNIVERSITÄTSKLINIKUM HEIDELBERG Wkład UE Brak danych Adres Im Neuenheimer Feld 672 HEIDELBERG Niemcy Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych Uczestnicy (4) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko UNIVERSITY OF GLASGOW Zjednoczone Królestwo Wkład UE Brak danych Adres University Avenue GLASGOW Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych EIDGENÖSSISCHE TECHNISCHE HOCHSCHULE ZÜRICH Szwajcaria Wkład UE Brak danych Adres Raemistrasse 101 ZÜRICH Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych TECHNISCHE UNIVERSITÄT GRAZ Austria Wkład UE Brak danych Adres Rechbauerstr. 12 GRAZ Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych RUPRECHT-KARLS-UNIVERSITÄT HEIDELBERG Niemcy Wkład UE Brak danych Adres Seminarstr. 2 HEIDELBERG Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych
