4nun
Crystal structure of copper-bound Na-ASP-2
Structural highlights
FunctionPublication Abstract from PubMedHookworm 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. Probing the equatorial groove of the hookworm protein and vaccine candidate antigen, Na-ASP-2.,Mason L, Tribolet L, Simon A, von Gnielinski N, Nienaber L, Taylor P, Willis C, Jones MK, Sternberg PW, Gasser RB, Loukas A, Hofmann A Int J Biochem Cell Biol. 2014 May;50:146-55. doi: 10.1016/j.biocel.2014.03.003., Epub 2014 Mar 13. PMID:24631931[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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