5TIV

Schistosoma haematobium (Blood Fluke) Sulfotransferase

Summary for 5TIV

• Entry DOI: 10.2210/pdb5tiv/pdb
• Related: 5TIW 5TIX 5TIY 5TIZ
• Descriptor: Sulfotransferase, ADENOSINE-3'-5'-DIPHOSPHATE, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• Functional Keywords: sulfotransferase, parasite, helminth, transferase
• Biological source: Schistosoma haematobium (Blood fluke)
• Total number of polymer chains: 1
• Total formula weight: 29811.91

Authors

Taylor, A.B.,Hart, P.J. (deposition date: 2016-10-03, release date: 2017-05-31, Last modification date: 2023-10-04)

Primary citation

Taylor, A.B.,Roberts, K.M.,Cao, X.,Clark, N.E.,Holloway, S.P.,Donati, E.,Polcaro, C.M.,Pica-Mattoccia, L.,Tarpley, R.S.,McHardy, S.F.,Cioli, D.,LoVerde, P.T.,Fitzpatrick, P.F.,Hart, P.J.
Structural and enzymatic insights into species-specific resistance to schistosome parasite drug therapy.
J. Biol. Chem., 292:11154-11164, 2017

PubMed Abstract: The antischistosomal prodrug oxamniquine is activated by a sulfotransferase (SULT) in the parasitic flatworm Of the three main human schistosome species, only is sensitive to oxamniquine therapy despite the presence of SULT orthologs in and The reason for this species-specific drug action has remained a mystery for decades. Here we present the crystal structures of and SULTs, including SULT in complex with oxamniquine. We also examined the activity of the three enzymes ; surprisingly, all three are active toward oxamniquine, yet we observed differences in catalytic efficiency that implicate kinetics as the determinant for species-specific toxicity. These results provide guidance for designing oxamniquine derivatives to treat infection caused by all species of schistosome to combat emerging resistance to current therapy.

PubMed: 28536265
DOI: 10.1074/jbc.M116.766527

Experimental method

X-RAY DIFFRACTION (1.43 Å)