Molecular insights into the interaction between plasmodium falciparum apical membrane antigen 1 and an invasion-inhibitory peptide

Wang, Geqing, MacRaild, Christopher A., Mohanty, Biswaranjan, Mobli, Mehdi, Cowieson, Nathan P., Anders, Robin F., Simpson, Jamie S., McGowan, Sheena, Norton, Raymond S. and Scanlon, Martin J. (2014) Molecular insights into the interaction between plasmodium falciparum apical membrane antigen 1 and an invasion-inhibitory peptide. PLoS One, 9 10: 1-12. doi:10.1371/journal.pone.0109674


Author Wang, Geqing
MacRaild, Christopher A.
Mohanty, Biswaranjan
Mobli, Mehdi
Cowieson, Nathan P.
Anders, Robin F.
Simpson, Jamie S.
McGowan, Sheena
Norton, Raymond S.
Scanlon, Martin J.
Title Molecular insights into the interaction between plasmodium falciparum apical membrane antigen 1 and an invasion-inhibitory peptide
Formatted title
Molecular insights into the interaction between plasmodium falciparum apical membrane antigen 1 and an invasion-inhibitory peptide
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2014-10-24
Year available 2014
Sub-type Article (original research)
DOI 10.1371/journal.pone.0109674
Open Access Status DOI
Volume 9
Issue 10
Start page 1
End page 12
Total pages 12
Place of publication San Francisco, United States
Publisher Public Library of Science
Collection year 2015
Language eng
Formatted abstract
Apical membrane antigen 1 (AMA1) of the human malaria parasite Plasmodium falciparum has been implicated in invasion of the host erythrocyte. It interacts with malarial rhoptry neck (RON) proteins in the moving junction that forms between the host cell and the invading parasite. Agents that block this interaction inhibit invasion and may serve as promising leads for anti-malarial drug development. The invasion-inhibitory peptide R1 binds to a hydrophobic cleft on AMA1, which is an attractive target site for small molecules that block parasite invasion. In this work, truncation and mutational analyses show that Phe5-Phe9, Phe12 and Arg15 in R1 are the most important residues for high affinity binding to AMA1. These residues interact with two well-defined binding hot spots on AMA1. Computational solvent mapping reveals that one of these hot spots is suitable for small molecule targeting. We also confirm that R1 in solution binds to AMA1 with 1:1 stoichiometry and adopts a secondary structure consistent with the major form of R1 observed in the crystal structure of the complex. Our results provide a basis for designing high affinity inhibitors of the AMA1-RON2 interaction.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e109674

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Centre for Advanced Imaging Publications
 
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Created: Thu, 20 Nov 2014, 10:13:45 EST by Shona Osborne on behalf of Centre for Advanced Imaging