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| | <StructureSection load='6uuy' size='340' side='right'caption='[[6uuy]], [[Resolution|resolution]] 1.37Å' scene=''> | | <StructureSection load='6uuy' size='340' side='right'caption='[[6uuy]], [[Resolution|resolution]] 1.37Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6uuy]] is a 2 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=6UUY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UUY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6uuy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_haematobium Schistosoma haematobium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UUY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UUY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A3P:ADENOSINE-3-5-DIPHOSPHATE'>A3P</scene>, <scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=QHM:hycanthone'>QHM</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.37Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MS3_07706 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6185 Blood fluke])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A3P:ADENOSINE-3-5-DIPHOSPHATE'>A3P</scene>, <scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=QHM:hycanthone'>QHM</scene></td></tr> |
| - | <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=6uuy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uuy OCA], [http://pdbe.org/6uuy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uuy RCSB], [http://www.ebi.ac.uk/pdbsum/6uuy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uuy ProSAT]</span></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=6uuy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uuy OCA], [https://pdbe.org/6uuy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uuy RCSB], [https://www.ebi.ac.uk/pdbsum/6uuy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uuy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A094ZWQ2_SCHHA A0A094ZWQ2_SCHHA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6uuy" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6uuy" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Sulfotransferase 3D structures|Sulfotransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Blood fluke]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Taylor, A B]] | + | [[Category: Schistosoma haematobium]] |
| - | [[Category: Drug resistance]] | + | [[Category: Taylor AB]] |
| - | [[Category: Hycanthone]]
| + | |
| - | [[Category: Parasite]]
| + | |
| - | [[Category: Schistosome]]
| + | |
| - | [[Category: Sulfotransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
6uuy is a 2 chain structure with sequence from Schistosoma haematobium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.37Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
A0A094ZWQ2_SCHHA
Publication Abstract from PubMed
Hycanthone (HYC) is a retired drug formerly used to treat schistosomiasis caused by infection from Schistosoma mansoni and S. haematobium. Resistance to HYC was first observed in S. mansoni laboratory strains and in patients in the 1970s and the use of this drug was subsequently discontinued with the substitution of praziquantel (PZQ) as the single antischistosomal drug in the worldwide formulary. In endemic regions, multiple organizations have partnered with the World Health Organization to deliver PZQ for morbidity control and prevention. While the monotherapy reduces the disease burden, additional drugs are needed to use in combination with PZQ to stay ahead of potential drug resistance. HYC will not be reintroduced into the schistosomiasis drug formulary as a combination drug because it was shown to have adverse properties including mutagenic, teratogenic and carcinogenic activities. Oxamniquine (OXA) was used to treat S. mansoni infection in Brazil during the brief period of HYC use, until the 1990s. Its antischistosomal efficacy has been shown to work through the same mechanism as HYC and it does not possess the undesirable properties linked to HYC. OXA demonstrates cross-resistance in Schistosoma strains with HYC resistance and both are prodrugs requiring metabolic activation in the worm to toxic sulfated forms. The target activating enzyme has been identified as a sulfotransferase enzyme and is currently used as the basis for a structure-guided drug design program. Here, we characterize the sulfotransferases from S. mansoni and S. haematobium in complexes with HYC to compare and contrast with OXA-bound sulfotransferase crystal structures. Although HYC is discontinued for antischistosomal treatment, it can serve as a resource for design of derivative compounds without contraindication.
Molecular basis for hycanthone drug action in schistosome parasites.,Guzman M, Rugel A, Tarpley RS, Cao X, McHardy SF, LoVerde PT, Taylor AB Mol Biochem Parasitol. 2020 Feb 3;236:111257. doi:, 10.1016/j.molbiopara.2020.111257. PMID:32027942[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Guzman M, Rugel A, Tarpley RS, Cao X, McHardy SF, LoVerde PT, Taylor AB. Molecular basis for hycanthone drug action in schistosome parasites. Mol Biochem Parasitol. 2020 Feb 3;236:111257. doi:, 10.1016/j.molbiopara.2020.111257. PMID:32027942 doi:http://dx.doi.org/10.1016/j.molbiopara.2020.111257
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