Abstract:
The crystal structure of GST Nu2-2 (HpolGSTN2-2) from the model hookworm nematode Heligmosomoides polygyrus has been solved by the molecular replacement method and refined to a resolution of 1.71 Å, providing the first structural data from a class of nematode-specific GSTs. By structural alignment with two Sigma class GSTs, glutathione could be rationally docked into the G-site of the enzyme. By comparing with all mammalian GST classes, a novel, long, and deep cleft was identified at the H-site, providing a potential site for ligand binding. This new GST class may support the establishment of infection parasitic nematodes by passively neutralizing chemical toxins derived from host environment. The structure serves as a starting point for structure-based drug/inhibitor design that would aim to selectively disrupt nematode chemical defenses.
Description:
Schuller, D. J., Liu, Q., Kriksunov, I. A., Campbell, A. M., Barrett, J., Brophy, P. M., Hao, Q. (2005). Crystal structure of a new class of glutathione transferase from the model human hookworm ematode Heligmosomoides polygyrus. Proteins: Structure Function and Bioinformatics, 61, (4), 1024-1031. Sponsorship: BBSRC UK-Grant Number: S14953/ National Institutes of Health (National Center for Research Resources)-Grant Number: RR-01646/ National Science Foundation - Grant Number: DMR 02-25180.