View source for 4z09


==Crystal structure of FVO strain Plasmodium falciparum AMA1 in complex with the RON2hp [Thr2040Ala] peptide==
<StructureSection load='4z09' size='340' side='right'caption='[[4z09]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4z09]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum_Vietnam_Oak-Knoll_(FVO) Plasmodium falciparum Vietnam Oak-Knoll (FVO)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z09 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z09 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4z09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z09 OCA], [https://pdbe.org/4z09 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z09 RCSB], [https://www.ebi.ac.uk/pdbsum/4z09 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z09 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A024UZE1_PLAFA A0A024UZE1_PLAFA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The interaction between apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2) plays a key role in the invasion of red blood cells by Plasmodium parasites. Disruption of this critical protein-protein interaction represents a promising avenue for antimalarial drug discovery. In this work, we exploited a 13-residue beta-hairpin based on the C-terminal loop of RON2 to probe a conserved binding site on Plasmodium falciparum AMA1. A series of mutations was synthetically engineered into beta-hairpin peptides to establish structure-activity relationships. The best mutations improved the binding affinity of the beta-hairpin peptide by ~7-fold for 3D7 AMA1 and ~14-fold for FVO AMA1. We determined the crystal structures of several beta-hairpin peptides in complex with AMA1 in order to define the structural features and specific interactions that contribute to improved binding affinity. The same mutations in the longer RON2sp2 peptide (residues 2027-2055 of RON2) increased the binding affinity by &gt;30-fold for 3D7 and FVO AMA1, producing KD values of 2.1nM and 0.4nM, respectively. To our knowledge, this is the most potent strain-transcending peptide reported to date and represents a valuable tool to characterize the AMA1-RON2 interaction.

Structure-Activity Studies of beta-Hairpin Peptide Inhibitors of the Plasmodium falciparum AMA1-RON2 Interaction.,Wang G, Drinkwater N, Drew DR, MacRaild CA, Chalmers DK, Mohanty B, Lim SS, Anders RF, Beeson JG, Thompson PE, McGowan S, Simpson JS, Norton RS, Scanlon MJ J Mol Biol. 2016 Jul 14. pii: S0022-2836(16)30246-7. doi:, 10.1016/j.jmb.2016.07.001. PMID:27422009<ref>PMID:27422009</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4z09" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: McGowan S]]
[[Category: Norton RS]]
[[Category: Scanlon MJ]]
[[Category: Wang G]]