4NUI

Crystal structure of cobalt-bound Na-ASP-2

Summary for 4NUI

• Entry DOI: 10.2210/pdb4nui/pdb
• Related: 4NUK 4NUN 4NUO
• Descriptor: Ancylostoma secreted protein 2, COBALT (II) ION (3 entities in total)
• Functional Keywords: scp/taps, excretory/secretory product, unknown function
• Biological source: Necator americanus (Human hookworm)
• Total number of polymer chains: 1
• Total formula weight: 22710.95

Authors

Hofmann, A. (deposition date: 2013-12-03, release date: 2014-05-14, Last modification date: 2023-09-20)

Primary citation

Mason, L.,Tribolet, L.,Simon, A.,von Gnielinski, N.,Nienaber, L.,Taylor, P.,Willis, C.,Jones, M.K.,Sternberg, P.W.,Gasser, R.B.,Loukas, A.,Hofmann, A.
Probing the equatorial groove of the hookworm protein and vaccine candidate antigen, Na-ASP-2.
Int.J.Biochem.Cell Biol., 50:146-155, 2014

PubMed 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.

PubMed: 24631931
DOI: 10.1016/j.biocel.2014.03.003

Experimental method

X-RAY DIFFRACTION (1.7 Å)