Analysis of active site loop amino asids of enzyme plasmodium vivax lactate dehydrogenase in by site-directed mutagenesis studies

ABSTRACTMASTER THESISANALYSIS OF ACTIVITE SITE LOOP AMINO ACIDS OF ENZYMEPlasmodium vivax LACTATE DEHYDROGENASE IN BY SITE-DIRECTED MUTAGENESIS STUDIESDilek SADAKFirat UniversityGraduate School of Natural and Applied SciencesDepartment of Biology2006, Page: 48Increasing resistance of malaria parasites to the currently available drugs necessitatesthe development of new antimalarials. In this thesis, glycolytic enzyme lactate dehydrogenaseof Plasmodium vivax has been targetted for this aim. Active site loop of this enzyme is extendedby five extra amino acids. The extended loop is not present in their human counterpart. Incombination to the kinetic studies, this makes the site an ideal target for the structure based drugdesign studies. Lactate dehydrogenase was evaluated from Plasmodium vivax by the sitedirected mutagenesis studies in this thesis. The enzyme remained active after the removal of thefirst two amino acids from the loop, but this activity abolished when all of the inserted aminoacids were removed. These results supports the idea of being this site ideal target for the designof new antimalarials.Keywords: Plasmodium vivax, lactate dehydrogenase, active site loop, site directedmutagenesis, antimalarial.