Probing the equatorial groove of the hookworm protein and vaccine candidate antigen, Na-ASP-2

Mason, Lyndel, Tribolet, Leon, Simon, Anne, Von Gnielinski, Natascha, Nienaber, Lisa, Taylor, Paul, Willis, Charlene, Jones, Malcolm K., Sternberg, Paul W., Gasser, Robin B., Loukas, Alex and Hofmann, Andreas (2014) Probing the equatorial groove of the hookworm protein and vaccine candidate antigen, Na-ASP-2. International Journal of Biochemistry and Cell Biology, 50 1: 146-155. doi:10.1016/j.biocel.2014.03.003


Author Mason, Lyndel
Tribolet, Leon
Simon, Anne
Von Gnielinski, Natascha
Nienaber, Lisa
Taylor, Paul
Willis, Charlene
Jones, Malcolm K.
Sternberg, Paul W.
Gasser, Robin B.
Loukas, Alex
Hofmann, Andreas
Title Probing the equatorial groove of the hookworm protein and vaccine candidate antigen, Na-ASP-2
Journal name International Journal of Biochemistry and Cell Biology   Check publisher's open access policy
ISSN 1357-2725
1878-5875
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.biocel.2014.03.003
Open Access Status DOI
Volume 50
Issue 1
Start page 146
End page 155
Total pages 10
Place of publication Cambridge, MA United States
Publisher Elsevier Ltd
Language eng
Subject 1303 Specialist Studies in Education
1307 Cell Biology
Abstract Hookworm activation-associated secreted proteins can be structurally classified into at least three different groups. The hallmark feature of Group 1 activation-associated secreted proteins is a prominent equatorial groove, which is inferred to form a ligand binding site. Furthermore, a conserved tandem histidine motif is located in the centre of the groove and believed to provide or support a yet to be determined catalytic activity. Here, we report three-dimensional crystal structures of Na-ASP-2, an L3-secreted activation-associated secreted protein from the human hookworm Necator americanus, which demonstrate transition metal binding ability of the conserved tandem histidine motif. We further identified moderate phosphohydrolase activity of recombinant Na-ASP-2, which relates to the tandem histidine motif. By panning a random 12-mer peptide phage library, we identified a peptide with high similarity to the human calcium-activated potassium channel SK3, and confirm binding of the synthetic peptide to recombinant Na-ASP-2 by differential scanning fluorimetry. Potential binding modes of the peptide to Na-ASP-2 were studied by molecular dynamics simulations which clearly identify a preferred topology of the Na-ASP-2:SK3 peptide complex.
Keyword Activation associated secreted proteins
Host parasite interactions
Pathogenesis related proteins
Protein structure
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Veterinary Science Publications
 
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