View source for 6rwd


==Crystal structure of SjGST in complex with GSH and ellagic acid at 1.53 Angstrom resolution==
<StructureSection load='6rwd' size='340' side='right'caption='[[6rwd]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rwd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_japonicum Schistosoma japonicum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RWD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RWD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.53&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=REF:2,3,7,8-TETRAHYDROXYCHROMENO[5,4,3-CDE]CHROMENE-5,10-DIONE'>REF</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6rwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rwd OCA], [https://pdbe.org/6rwd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rwd RCSB], [https://www.ebi.ac.uk/pdbsum/6rwd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rwd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GST26_SCHJA GST26_SCHJA] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.  GST isoenzymes appear to play a central role in the parasite detoxification system. Other functions are also suspected including a role in increasing the solubility of haematin in the parasite gut.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 IC50 of 2.4 muM. 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 (DeltaG = -29.88 +/- 0.07 kJ/mol), enthalpically-driven (DeltaH = -9.48 +/- 0.42 kJ/mol) with a favourable entropic change (DeltaS = 20.40 +/- 0.08 kJ/mol/K), and with a stoichiometry of four EA molecules bound per Sj26GST dimer. The 1.53 A-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 A from the epsilon-NH2 of the gamma-glutamyl moiety of GSH, in each subunit.

Molecular basis of inhibition of Schistosoma japonicum glutathione transferase by ellagic acid: Insights into biophysical and structural studies.,Akumadu BO, Pandian R, Olfsen J, Worth R, Thulo M, Mentor T, Fanucchi S, Sayed Y, Dirr HW, Achilonu I Mol Biochem Parasitol. 2020 Sep 19;240:111319. doi:, 10.1016/j.molbiopara.2020.111319. PMID:32961204<ref>PMID:32961204</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rwd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Schistosoma japonicum]]
[[Category: Achilonu IA]]
[[Category: Dirr HW]]
[[Category: Olfsen J]]
[[Category: Pandian R]]
[[Category: Sayed Y]]