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4MUB

Schistosoma mansoni (Blood Fluke) Sulfotransferase/Oxamniquine Complex

Summary for 4MUB
Entry DOI10.2210/pdb4mub/pdb
DescriptorSulfotransferase, ADENOSINE-3'-5'-DIPHOSPHATE, {(2S)-7-nitro-2-[(propan-2-ylamino)methyl]-1,2,3,4-tetrahydroquinolin-6-yl}methanol, ... (4 entities in total)
Functional Keywordspap, oxamniquine, parasite, helminth, drug resistance, transferase
Biological sourceSchistosoma mansoni (Blood fluke)
Total number of polymer chains1
Total formula weight30683.10
Authors
Primary citationValentim, C.L.,Cioli, D.,Chevalier, F.D.,Cao, X.,Taylor, A.B.,Holloway, S.P.,Pica-Mattoccia, L.,Guidi, A.,Basso, A.,Tsai, I.J.,Berriman, M.,Carvalho-Queiroz, C.,Almeida, M.,Aguilar, H.,Frantz, D.E.,Hart, P.J.,LoVerde, P.T.,Anderson, T.J.
Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites.
Science, 342:1385-1389, 2013
Cited by
PubMed Abstract: 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 >99% of schistosomiasis cases worldwide.
PubMed: 24263136
DOI: 10.1126/science.1243106
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.75 Å)
Structure validation

231029

數據於2025-02-05公開中

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