Structure of glutathione S-transferase of the filarial parasite Wuchereria bancrofti: a target for drug development against adult worm.
A three dimensional structural model of Glutathione-S-transferase (GST) of the lymphatic filarial parasite Wuchereria bancrofti (wb) was constructed by homology modeling. The three dimensional X-ray crystal structure of porcine pi-class GST with PDB ID: 2gsr-A chain protein with 42% sequential and functional homology was used as the template. The model of wbGST built by MODELLER6v2 was analyzed by the PROCHECK programs. Ramachandran plot analysis showed that 93.5% of the residues are in the core region followed by 5.4 and 1.1% residues in the allowed and generously allowed regions, respectively. None of the non-glycine residues is in disallowed regions. The PROSA II z-score and the energy graph for the final model further confirmed the quality of the modeled structure. The computationally modeled three-dimensional (3D) structure of wbGST has been submitted to the Protein Data Bank (PDB) (PDB ID: 1SFM and RCSB ID: RCSB021668). 1SFM was used for docking with GST inhibitors by Hex4.2 macromolecular docking using spherical polar Fourier correlations.
Nathan
Sivaramakrishnan Thirumalai
ST
Vector Control Research Centre, Indian Council of Medical Research, Indira Nagar, Pondicherry, 605006, India.
Mathew
Nisha
N
Kalyanasundaram
Muthuswami
M
Balaraman
Kothandapani
K
D000596:Amino Acids; D000818:Animals; D000969:Antinematodal Agents; D001665:Binding Sites; D015195:Drug Design; D005978:Glutathione / Q000031:analogs & derivatives; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D015801:Helminth Proteins / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D012984:Software; D014958:Wuchereria bancrofti / Q000201:enzymology*
D000596:Amino Acids; D000969:Antinematodal Agents; D015801:Helminth Proteins; D008024:Ligands; D005982:Glutathione Transferase; D005978:Glutathione