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| | ==Structure of the Aldose Reductase from Schistosoma japonicum== | | ==Structure of the Aldose Reductase from Schistosoma japonicum== |
| - | <StructureSection load='4hbk' size='340' side='right' caption='[[4hbk]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='4hbk' size='340' side='right'caption='[[4hbk]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hbk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Blood_fluke Blood fluke]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HBK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HBK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hbk]] is a 1 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=4HBK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HBK FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Akr1b4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6182 Blood fluke])</td></tr> | + | </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=4hbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hbk OCA], [https://pdbe.org/4hbk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hbk RCSB], [https://www.ebi.ac.uk/pdbsum/4hbk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hbk ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aldehyde_reductase Aldehyde reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.21 1.1.1.21] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hbk OCA], [http://pdbe.org/4hbk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hbk RCSB], [http://www.ebi.ac.uk/pdbsum/4hbk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hbk ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q5DD64_SCHJA Q5DD64_SCHJA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Aldose Reductase|Aldose Reductase]] | + | *[[Aldo-keto reductase 3D structures|Aldo-keto reductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aldehyde reductase]] | + | [[Category: Large Structures]] |
| - | [[Category: Blood fluke]] | + | [[Category: Schistosoma japonicum]] |
| - | [[Category: Cheng, J]] | + | [[Category: Cheng J]] |
| - | [[Category: Hu, W]] | + | [[Category: Hu W]] |
| - | [[Category: Liu, J]] | + | [[Category: Liu J]] |
| - | [[Category: Xu, Y]] | + | [[Category: Xu Y]] |
| - | [[Category: Yang, Z]] | + | [[Category: Yang Z]] |
| - | [[Category: Zhang, X]] | + | [[Category: Zhang X]] |
| - | [[Category: Aldose reductase]]
| + | |
| - | [[Category: Oxidoreductase]]
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| Structural highlights
Function
Q5DD64_SCHJA
Publication Abstract from PubMed
BACKGROUND: Schistosomiasis is a neglected tropical disease with high morbidity and mortality in the world. Currently, the treatment of this disease depends almost exclusively on praziquantel (PZQ); however, the emergence of drug resistance to PZQ in schistosomes makes the development of novel drugs an urgent task. Aldose reductase (AR), an important component that may be involved in the schistosome antioxidant defense system, is predicted as a potential drug target. METHODS: The tertiary structure of Schistosoma japonicum AR (SjAR) was obtained through X-ray diffraction method and then its potential inhibitors were identified from the Maybridge HitFinder library by virtual screening based on this structural model. The effects of these identified compounds on cultured adult worms were evaluated by observing mobility, morphological changes and mortality. To verify that SjAR was indeed the target of these identified compounds, their effects on recombinant SjAR (rSjAR) enzymatic activity were assessed. The cytotoxicity analysis was performed with three types of human cell lines using a Cell Counting Kit-8. RESULTS: We firstly resolved the SjAR structure and identified 10 potential inhibitors based on this structural model. Further in vitro experiments showed that one of the compounds, renamed as AR9, exhibited significant inhibition in the activity of cultured worms as well as inhibition of enzymatic activity of rSjAR protein. Cytotoxicity analysis revealed that AR9 had relatively low toxicity towards host cells. CONCLUSIONS: The work presented here bridges the gap between virtual screening and experimental validation, providing an effective and economical strategy for the development of new anti-parasitic drugs. Additionally, this study also found that AR9 may become a new potential lead compound for developing novel antischistosomal drugs against parasite AR.
Aldose reductase from Schistosoma japonicum: crystallization and structure-based inhibitor screening for discovering antischistosomal lead compounds.,Liu J, Dyer DH, Cheng J, Wang J, Wang S, Yang Z, Wang X, Hu W Parasit Vectors. 2013 Jun 5;6:162. doi: 10.1186/1756-3305-6-162. PMID:23734964[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu J, Dyer DH, Cheng J, Wang J, Wang S, Yang Z, Wang X, Hu W. Aldose reductase from Schistosoma japonicum: crystallization and structure-based inhibitor screening for discovering antischistosomal lead compounds. Parasit Vectors. 2013 Jun 5;6:162. doi: 10.1186/1756-3305-6-162. PMID:23734964 doi:10.1186/1756-3305-6-162
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