{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T23:14:15Z","timestamp":1789859655136,"version":"4.0.1"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Schistosomiasis affects over 200 million people worldwide, with over 200,000 deaths annually. Currently, praziquantel is the only drug available against schistosomiasis. We report here that\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Schistosoma mansoni<\/jats:named-content>\n            farnesyl diphosphate synthase (\n            <jats:italic>Sm<\/jats:italic>\n            FPPS) and geranylgeranyl diphosphate synthase (\n            <jats:italic>Sm<\/jats:italic>\n            GGPPS) are potential drug targets for the treatment of schistosomiasis. We expressed active, recombinant\n            <jats:italic>Sm<\/jats:italic>\n            FPPS and\n            <jats:italic>Sm<\/jats:italic>\n            GGPPS for subsequent kinetic characterization and testing against a variety of bisphosphonate inhibitors. Recombinant\n            <jats:italic>Sm<\/jats:italic>\n            FPPS was found to be a soluble 44.2-kDa protein, while\n            <jats:italic>Sm<\/jats:italic>\n            GGPPS was a soluble 38.3-kDa protein. Characterization of the substrate utilization of the two enzymes indicates that they have overlapping substrate specificities. Against\n            <jats:italic>Sm<\/jats:italic>\n            FPPS, several bisphosphonates had 50% inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            s) in the low micromolar to nanomolar range; these inhibitors had significantly less activity against\n            <jats:italic>Sm<\/jats:italic>\n            GGPPS. Several lipophilic bisphosphonates were active against\n            <jats:italic>ex vivo<\/jats:italic>\n            adult worms, with worm death occurring over 4 to 6 days. These results indicate that FPPS and GGPPS could be of interest in the context of the emerging resistance to praziquantel in schistosomiasis therapy.\n          <\/jats:p>","DOI":"10.1128\/aac.00699-13","type":"journal-article","created":{"date-parts":[[2013,9,17]],"date-time":"2013-09-17T03:45:54Z","timestamp":1379389554000},"page":"5969-5976","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Characterization of Potential Drug Targets Farnesyl Diphosphate Synthase and Geranylgeranyl Diphosphate Synthase in Schistosoma mansoni"],"prefix":"10.1128","volume":"57","author":[{"given":"Peter D.","family":"Ziniel","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Illinois State University, Normal, Illinois, USA"},{"name":"Department of Immunology\/Microbiology, Rush University Medical Center, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janish","family":"Desai","sequence":"additional","affiliation":[{"name":"Center for Biophysics and Computational Biology, University of Illinois, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia L.","family":"Cass","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Illinois State University, Normal, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Gatto","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Illinois State University, Normal, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Oldfield","sequence":"additional","affiliation":[{"name":"Center for Biophysics and Computational Biology, University of Illinois, Urbana, Illinois, USA"},{"name":"Department of Chemistry, University of Illinois, Urbana, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Williams","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Illinois State University, Normal, Illinois, USA"},{"name":"Department of Immunology\/Microbiology, Rush University Medical Center, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60233-6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(06)70521-7"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-012-3151-z"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201000202"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2013.01.003"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00169467"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.157"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.61.070192.002035"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar100026v"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201103110"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.26.120192.001233"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(70)90170-0"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08160"},{"key":"e_1_3_3_15_2","first-page":"R618","article-title":"Physiological role of HMG-CoA reductase in regulating egg production by Schistosoma mansoni","volume":"257","author":"Vandewaa EA","year":"1989","unstructured":"VandewaaEA MillsG ChenGZ FosterLA BennettJL. 1989. Physiological role of HMG-CoA reductase in regulating egg production by Schistosoma mansoni. Am. J. Physiol. 257:R618\u2013R625.","journal-title":"Am. J. Physiol."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.21.8217"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(93)90226-N"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(93)90073-7"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(99)00029-8"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(96)02579-0"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(03)00046-8"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.7.3957"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)38120-6"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3513311"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762008000500007"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1346.041"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0002578"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-6-60"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1468"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0102809"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103950200"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210467200"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5009"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm030084x"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.12.3.253"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01820-10"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm8009074"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00198-10"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1901s28"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)32030-6"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)32159-3"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040206"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00202a004"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvg002"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi3005335"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03583.x"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.12.094"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.2"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.68.2360"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.027235"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2008.10.017"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2007.057"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja808285e"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200905933"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00699-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00699-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:28:18Z","timestamp":1645482498000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00699-13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12]]},"references-count":53,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["10.1128\/AAC.00699-13"],"URL":"https:\/\/doi.org\/10.1128\/aac.00699-13","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12]]},"assertion":[{"value":"2013-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-09-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-11-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}