5byk | pdb_00005byk

Schistosoma mansoni (Blood Fluke) Sulfotransferase/S-oxamniquine Complex

spinqualitylabelsall models 5byk, resolution 1.28Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5byk is a 1 chain structure with sequence from Schistosoma mansoni. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.28Å Ligands: A3P, CAS, NA, OAQ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G4VLE5_SCHMA Publication Abstract from PubMed BACKGROUND: 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Sulfotransferase 3D structures

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