5byk: Difference between revisions
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==Schistosoma mansoni (Blood Fluke) Sulfotransferase/S-oxamniquine Complex== | ==Schistosoma mansoni (Blood Fluke) Sulfotransferase/S-oxamniquine Complex== | ||
<StructureSection load='5byk' size='340' side='right' caption='[[5byk]], [[Resolution|resolution]] 1.28Å' scene=''> | <StructureSection load='5byk' size='340' side='right'caption='[[5byk]], [[Resolution|resolution]] 1.28Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5byk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BYK FirstGlance]. <br> | <table><tr><td colspan='2'>[[5byk]] 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=5BYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BYK 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=NA:SODIUM+ION'>NA</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='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=NA:SODIUM+ION'>NA</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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5byj|5byj]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5byj|5byj]]</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=5byk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5byk OCA], [http://pdbe.org/5byk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5byk RCSB], [http://www.ebi.ac.uk/pdbsum/5byk PDBsum]</span></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='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=5byk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5byk OCA], [http://pdbe.org/5byk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5byk RCSB], [http://www.ebi.ac.uk/pdbsum/5byk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5byk ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5byk" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5byk" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Sulfotransferase|Sulfotransferase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Blood fluke]] | |||
[[Category: Large Structures]] | |||
[[Category: Cao, X]] | [[Category: Cao, X]] | ||
[[Category: Hart, P J]] | [[Category: Hart, P J]] | ||
Revision as of 14:04, 18 March 2020
Schistosoma mansoni (Blood Fluke) Sulfotransferase/S-oxamniquine ComplexSchistosoma mansoni (Blood Fluke) Sulfotransferase/S-oxamniquine Complex
Structural highlights
Publication Abstract from PubMedBACKGROUND: For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a ~30 kDa S. mansoni sulfotransferase (SmSULT) was identified as the target of OXA action. METHODOLOGY/PRINCIPAL FINDINGS: Here, we separate the OXA enantiomers using chromatographic methods and assign their optical activities as dextrorotary [(+)-OXA] or levorotary [(-)-OXA]. Crystal structures of the parasite enzyme in complex with optically pure (+)-OXA and (-)-OXA) reveal their absolute configurations as S- and R-, respectively. When tested in vitro, S-OXA demonstrated the bulk of schistosomicidal activity, while R-OXA had antischistosomal effects when present at relatively high concentrations. Crystal structures R-OXA*SmSULT and S-OXA*SmSULT complexes reveal similarities in the modes of OXA binding, but only the S-OXA enantiomer is observed in the structure of the enzyme exposed to racemic OXA. CONCLUSIONS/SIGNIFICANCE: Together the data suggest the higher schistosomicidal activity of S-OXA is correlated with its ability to outcompete R-OXA binding the sulfotransferase active site. These findings have important implications for the design, syntheses, and dosing of new OXA-based antischistosomal compounds. Structural and Functional Characterization of the Enantiomers of the Antischistosomal Drug Oxamniquine.,Taylor AB, Pica-Mattoccia L, Polcaro CM, Donati E, Cao X, Basso A, Guidi A, Rugel AR, Holloway SP, Anderson TJ, Hart PJ, Cioli D, LoVerde PT PLoS Negl Trop Dis. 2015 Oct 20;9(10):e0004132. doi:, 10.1371/journal.pntd.0004132. eCollection 2015 Oct. PMID:26485649[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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