Crystal structure of a new class of glutathione transferase from the model human hookworm nematode Heligmosomoides polygyrus.
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 A, 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.
Schuller
David J
DJ
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853-8001, USA.
Liu
Qun
Q
Kriksunov
Irina A
IA
Campbell
Alison M
AM
Barrett
John
J
Brophy
Peter M
PM
Hao
Quan
Q
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D006369:Heligmosomatoidea / Q000201:enzymology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017206:Strongylida Infections
D004791:Enzyme Inhibitors; D008024:Ligands; D005982:Glutathione Transferase