TY  - JOUR
AU  - Rajaiah Prabhu, Prince
AU  - Moorthy, Sakthi Devi
AU  - Madhumathi, Jayaprakasam
AU  - Pradhan, Satya Narayan
AU  - Perbandt, Markus
AU  - Betzel, Christian
AU  - Kaliraj, Perumal
TI  - Wucherria bancrofti glutathione S-Transferase: Insights into the 2.3 Å resolution X-ray structure and function, a therapeutic target for human lymphatic filariasis
JO  - Biochemical and biophysical research communications
VL  - 505
IS  - 4
SN  - 0006-291X
CY  - Orlando, Fla.
PB  - Academic Press
M1  - PUBDB-2018-05492
SP  - 979 - 984
PY  - 2018
N1  - © Elsevier Inc.
AB  - The notoriety of parasitic nematode survival is directly related to chronic pathogenicity, which is evident in human lymphatic filariasis. It is a disease of poverty which causes severe disability affecting more than 120 million people worldwide. These nematodes down-regulate host immune system through a myriad of strategies that includes secretion of antioxidant and detoxification enzymes like glutathione-S-transferases (GSTs). Earlier studies have shown Wuchereria bancrofti GST to be a potential therapeutic target. Parasite GSTs catalyse the conjugation of glutathione to xenobiotic and other endogenous electrophiles and are essential for their long-term survival in lymph tissues. Hence, the crystal structure of WbGST along with its cofactor GSH at 2.3 Å resolution was determined. Structural comparisons against host GST reveal distinct differences in the substrate binding sites. The parasite xenobiotic binding site is more substrate/solvent accessible. The structure also suggests the presence of putative non-catalytic binding sites that may permit sequestration of endogenous and exogenous ligands. The structure of WbGST also provides a case for the role of the π-cation interaction in stabilizing catalytic Tyr compared to stabilization interactions described for other GSTs. Hence, the obtained information regarding crucial differences in the active sites will support future design of parasite specific inhibitors. Further, the study also evaluates the inhibition of WbGST and its variants by antifilarial diethylcarbamazine through kinetic assays.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000450019400004
C6  - pmid:30297111
DO  - DOI:10.1016/j.bbrc.2018.09.077
UR  - https://bib-pubdb1.desy.de/record/417259
ER  -