The malaria antigen apical membrane antigen 1 (AMA1) is a protein of the Plasmodium parasite that is involved in the formation of the moving junction during red blood cell infection (1). Thus, AMA1 has become a target for drug development (2). Here we describe the application of solution NMR spectroscopy to study AMA1-small molecule interactions. Based on perturbations in specific chemical shifts in the NMR spectrum of AMA1, it is feasible to map the binding sites for ligand/small inhibitory molecules, facilitating the design of new drugs to treat malaria.
AMA1 is a high molecular mass (42 kDa) protein, making its chemical shift analysis particularly challenging because of resonance overlap. We have used different labelling approaches including selective unlabelling to simplify and speed up the process of specific resonance assignments (3). The results from chemical shift analysis of AMA1 using selective unlabelling methods and other NMR approaches will be presented.