1U53

Novel X-Ray Structure of Na-ASP-2, a PR-1 protein from the nematode parasite Necator americanus and a vaccine antigen for human hookworm infection

Summary for 1U53

• Entry DOI: 10.2210/pdb1u53/pdb
• Related: 1CFE 1QNX
• Descriptor: secreted protein ASP-2 (2 entities in total)
• Functional Keywords: antibiotic
• Biological source: Necator americanus
• Total number of polymer chains: 1
• Total formula weight: 21214.12

Authors

Asojo, O.A.,Goud, G.,Dhar, K.,Loukas, A.,Zhan, B.,Deumic, V.,Liu, S.,Borgstahl, G.E.O.,Hotez, P.J. (deposition date: 2004-07-26, release date: 2005-02-01, Last modification date: 2024-11-06)

Primary citation

Asojo, O.A.,Goud, G.,Dhar, K.,Loukas, A.,Zhan, B.,Deumic, V.,Liu, S.,Borgstahl, G.E.,Hotez, P.J.
X-ray structure of Na-ASP-2, a pathogenesis-related-1 protein from the nematode parasite, Necator americanus, and a vaccine antigen for human hookworm infection.
J.Mol.Biol., 346:801-814, 2005

PubMed Abstract: Human hookworm infection is a major cause of anemia and malnutrition of adults and children in the developing world. As part of on-going efforts to control hookworm infection, The Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective L3 larval stages of the parasite, including a family of pathogenesis-related (PR) proteins known as the Ancylostoma-secreted proteins (ASPs). A novel crystal structure of Na-ASP-2, a PR-1 protein secreted by infective larvae of the human hookworm Necator americanus, has been solved to resolution limits of 1.68 A and to an R-factor of 17% using the recombinant protein expressed in and secreted by Pichia pastoris. The overall fold of Na-ASP-2 is a three-layer alphabetaalpha sandwich flanked by an N-terminal loop and a short, cysteine-rich C terminus. Our structure reveals a large central cavity that is flanked by His129 and Glu106, two residues that are well conserved in all parasitic nematode L3 ASPs. Na-ASP-2 has structural and charge similarities to chemokines, which suggests that Na-ASP-2 may be an extra-cellular ligand of an unknown receptor. Na-ASP-2 is a useful homology model for NIF, a natural antagonistic ligand of CR3 receptor. From these modeling studies, possible binding modes were predicted. In addition, this first structure of a PR-1 protein from parasitic helminths may shed light on the molecular basis of host-parasite interactions.

PubMed: 15713464
DOI: 10.1016/j.jmb.2004.12.023

Experimental method

X-RAY DIFFRACTION (1.56 Å)