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==Schistosoma mansoni (Blood Fluke) Sulfotransferase/Oxamniquine Complex==
==Schistosoma mansoni (Blood Fluke) Sulfotransferase/Oxamniquine Complex==
<StructureSection load='4mub' size='340' side='right' caption='[[4mub]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
<StructureSection load='4mub' size='340' side='right'caption='[[4mub]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4mub]] 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=4MUB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MUB FirstGlance]. <br>
<table><tr><td colspan='2'>[[4mub]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MUB 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=OAQ:{(2S)-7-NITRO-2-[(PROPAN-2-YLAMINO)METHYL]-1,2,3,4-TETRAHYDROQUINOLIN-6-YL}METHANOL'>OAQ</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]] 1.75&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Smp_089320 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6183 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=OAQ:{(2S)-7-NITRO-2-[(PROPAN-2-YLAMINO)METHYL]-1,2,3,4-TETRAHYDROQUINOLIN-6-YL}METHANOL'>OAQ</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=4mub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mub OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mub RCSB], [http://www.ebi.ac.uk/pdbsum/4mub PDBsum]</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=4mub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mub OCA], [https://pdbe.org/4mub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mub RCSB], [https://www.ebi.ac.uk/pdbsum/4mub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mub ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/G4VLE5_SCHMA G4VLE5_SCHMA]
Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing ~500-fold in drug response, determined drug sensitivity and marker segregation in clonally derived second-generation progeny, and identified a single quantitative trait locus (logarithm of odds = 31) on chromosome 6. A sulfotransferase was identified as the causative gene by using RNA interference knockdown and biochemical complementation assays, and we subsequently demonstrated independent origins of loss-of-function mutations in field-derived and laboratory-selected resistant parasites. These results demonstrate the utility of linkage mapping in a human helminth parasite, while crystallographic analyses of protein-drug interactions illuminate the mode of drug action and provide a framework for rational design of oxamniquine derivatives that kill both S. mansoni and S. haematobium, the two species responsible for &gt;99% of schistosomiasis cases worldwide.
 
Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites.,Valentim CL, Cioli D, Chevalier FD, Cao X, Taylor AB, Holloway SP, Pica-Mattoccia L, Guidi A, Basso A, Tsai IJ, Berriman M, Carvalho-Queiroz C, Almeida M, Aguilar H, Frantz DE, Hart PJ, LoVerde PT, Anderson TJ Science. 2013 Dec 13;342(6164):1385-9. doi: 10.1126/science.1243106. Epub 2013, Nov 21. PMID:24263136<ref>PMID:24263136</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Sulfotransferase|Sulfotransferase]]
*[[Sulfotransferase 3D structures|Sulfotransferase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Blood fluke]]
[[Category: Large Structures]]
[[Category: Aguilar, H]]
[[Category: Schistosoma mansoni]]
[[Category: Almeida, M]]
[[Category: Aguilar H]]
[[Category: Anderson, T J.C]]
[[Category: Almeida M]]
[[Category: Basso, A]]
[[Category: Anderson TJC]]
[[Category: Berriman, M]]
[[Category: Basso A]]
[[Category: Cao, X]]
[[Category: Berriman M]]
[[Category: Carvalho-Queiroz, C]]
[[Category: Cao X]]
[[Category: Chevalier, F D]]
[[Category: Carvalho-Queiroz C]]
[[Category: Cioli, D]]
[[Category: Chevalier FD]]
[[Category: Frantz, D E]]
[[Category: Cioli D]]
[[Category: Guidi, A]]
[[Category: Frantz DE]]
[[Category: Hart, P J]]
[[Category: Guidi A]]
[[Category: Holloway, S P]]
[[Category: Hart PJ]]
[[Category: LoVerde, P T]]
[[Category: Holloway SP]]
[[Category: Pica-Mattoccia, L]]
[[Category: LoVerde PT]]
[[Category: Taylor, A B]]
[[Category: Pica-Mattoccia L]]
[[Category: Tsai, I J]]
[[Category: Taylor AB]]
[[Category: Valentim, C L.L]]
[[Category: Tsai IJ]]
[[Category: Drug resistance]]
[[Category: Valentim CLL]]
[[Category: Helminth]]
[[Category: Oxamniquine]]
[[Category: Pap]]
[[Category: Parasite]]
[[Category: Transferase]]