Molecular Insights into the Interaction between <em>Plasmodium falciparum</em> Apical Membrane Antigen 1 and an Invasion-Inhibitory Peptide — ASN Events
  1. Schedule
  2. Session 5: Poster Session A
  3. Molecular Insights into the Interaction between Plasmodium falciparum Apical Membrane Antigen 1 and an Invasion-Inhibitory Peptide

Molecular Insights into the Interaction between Plasmodium falciparum Apical Membrane Antigen 1 and an Invasion-Inhibitory Peptide (#149)

Geqing Wang 1 , Chris A. MacRaild 1 , Biswaranjan Mohanty 1 2 , Mehdi Mobli 3 , Robin F. Anders 4 , Jamie S. Simpson 1 , Raymond S. Norton 1 , Martin J. Scanlon 1 2
  1. Monash Institute of Pharmaceutical Science, Parkville, VIC, Australia
  2. ARC Centre of Excellence for Coherent X-ray Science, Monash University, Melbourne, Australia
  3. Centre for Advanced Imaging, University of Queensland, St Lucia, Queensland, Australia
  4. Biochemistry, La Trobe University, Melbourne, VIC, Australia

Apical membrane antigen 1 (AMA1) is essential for efficient invasion of erythrocytes by malaria parasites and represents a promising target for anti-malarial drug development. 1 The peptide R1, which inhibits invasion by the malaria parasite, binds to a hydrophobic cleft on AMA1. 2 Truncation and mutational analyses show that Arg15 is the most important interacting residue in R1 binding to AMA1. The solution conformation of R1 bound to AMA1 was found to be similar to the higher affinity R1 binding site observed in the crystal structure of the complex. 3 Our results provide a basis for designing novel inhibitors of AMA1 interactions.

  1. Triglia, T., Healer, J., Caruana, S.R., Hodder, A.N., Anders, R.F., Crabb, B.S. and Cowman, A.F. (2000) Apical membrane antigen 1 plays a central role in erythrocyte invasion by Plasmodium species. Mol. Microbiol. 38, 706-18.
  2. Harris, K.S., Casey, J.L., Coley, A.M., Masciantonio, R., Sabo, J.K., Keizer, D.W., Lee, E.F., McMahon, A., Norton, R.S., Anders, R.F. and Foley, M. (2005) Binding hot spot for invasion inhibitory molecules on Plasmodium falciparum apical membrane antigen 1. Infect. Immun. 73, 6981-9.
  3. Vulliez-Le Normand, B., Tonkin, M.L., Lamarque, M.H., Langer, S., Hoos, S., Roques, M., Saul, F.A., Faber, B.W., Bentley, G.A., Boulanger, M.J. and Lebrun, M. (2012) Structural and functional insights into the malaria parasite moving junction complex. PLoS Pathog. 8, e1002755.