6RWD

Crystal structure of SjGST in complex with GSH and ellagic acid at 1.53 Angstrom resolution

Summary for 6RWD

• Entry DOI: 10.2210/pdb6rwd/pdb
• Related: 1UA5
• Descriptor: Glutathione S-transferase class-mu 26 kDa isozyme, GLUTATHIONE, SODIUM ION, ... (6 entities in total)
• Functional Keywords: schistosoma japonicum; sjgst; ellagic acid; gsh; 1.53ang, transferase
• Biological source: Schistosoma japonicum
• Total number of polymer chains: 2
• Total formula weight: 52103.17

Authors

Olfsen, J.,Pandian, R.,Sayed, Y.,Dirr, H.W.,Achilonu, I.A. (deposition date: 2019-06-04, release date: 2019-06-19, Last modification date: 2024-01-24)

Primary citation

Akumadu, B.O.,Pandian, R.,Olfsen, J.,Worth, R.,Thulo, M.,Mentor, T.,Fanucchi, S.,Sayed, Y.,Dirr, H.W.,Achilonu, I.
Molecular basis of inhibition of Schistosoma japonicum glutathione transferase by ellagic acid: Insights into biophysical and structural studies.
Mol.Biochem.Parasitol., 240:111319-111319, 2020

PubMed Abstract: Schistosoma japonicum glutathione transferase (Sj26GST), an enzyme central to detoxification of electrophilic compounds in the parasite, is upregulated in response to drug treatment. Therefore, Sj26GST may serve as a potential therapeutic target for the treatment of schistosomiasis. Herewith, we describe the structural basis of inhibition of Sj26GST by ellagic acid (EA). Using 1-chloro-2,4-dinitrobenzene and reduced glutathione (GSH) as Sj26GST substrates, EA was shown to inhibit Sj26GST activity by 66 % with an IC of 2.4 μM. Fluorescence spectroscopy showed that EA altered the polarity of the environment of intrinsic tryptophan and that EA decreased (in a dose-dependent manner) the interaction between Sj26GST and 8-Anilino-1-naphthalenesulfonate (ANS), which is a known GST H-site ligand. Thermodynamic studies indicated that the interaction between Sj26GST and EA is spontaneous (ΔG = -29.88 ± 0.07 kJ/mol), enthalpically-driven (ΔH = -9.48 ± 0.42 kJ/mol) with a favourable entropic change (ΔS = 20.40 ± 0.08 kJ/mol/K), and with a stoichiometry of four EA molecules bound per Sj26GST dimer. The 1.53 Å-resolution Sj26GST crystal structure (P 21 21 21 space group) complexed with GSH and EA shows that EA binds primarily at the dimer interface, stabilised largely by Van der Waal forces and H-bonding. Besides, EA bound near the H-site and less than 3.5 Å from the ε-NH of the γ-glutamyl moiety of GSH, in each subunit.

PubMed: 32961204
DOI: 10.1016/j.molbiopara.2020.111319

Experimental method

X-RAY DIFFRACTION (1.53 Å)