Objective Both dihydrofolate reductase-thymidylate synthase (DHR-TS) and DHFR from P. vivax will be cloned and expressed from E.coli. The kinetic properties of the expressed enzyme and the profiles of inhibition by various antifolates will be studied, in order to find out whether it is inherently resistant to inhibition. Mutants of P.vivax DHFR, both found in the field and artificially designed, as well as mutants of P.falciparum will be made and studied. The results will be used to model the three-dimensional structure of the enzymes, especially around the active site. Both DHFR and DHFR-TS from the two sources will be prepared in sufficient amounts for crystallization and structure determination by X-ray diffraction. Newly designed antifolates and those synthesized previously will be tested for their inhibitory activities. The mode of binding of such agents to the enzyme will be studied both from modelling and X-ray studies. Such agents will be important as leads to new antifolate drugs against both types of malaria. Agents with activity against both P. vivax and P.falciparum DHFR will be of special interest, in view of the common occurrence of mixed infections. Fields of science medical and health scienceshealth sciencesinfectious diseasesmalarianatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) FP5-INCO 2 - Programme for research, technological development and demonstration on "Confirming the international role of Community research,1998-2002" Topic(s) Data not available Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD EU contribution No data Address South Parks Road OX1 3QY OXFORD United Kingdom See on map Total cost No data Participants (3) Sort alphabetically Sort by EU Contribution Expand all Collapse all INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY India EU contribution No data Address Aruna Asaf Ali marg 10504 NEW DELHI See on map Links Website Opens in new window Total cost No data THAILAND NATIONAL SCIENCE AND TECHNOLOGY DEVELOPMENT AGENCY Thailand EU contribution No data Address Rama 6 Road 73-1 10400 BANGKOK See on map Total cost No data UNIVERSITY OF MODENA AND REGGIO EMILIA Italy EU contribution No data Address Via Campi 183 41100 MODENA See on map Total cost No data