{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:25:43Z","timestamp":1782512743339,"version":"3.54.5"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,8,28]],"date-time":"2012-08-28T00:00:00Z","timestamp":1346112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:italic><jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>rypanosoma brucei<\/jats:italic> is the causative agent of <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>frican sleeping sickness, putting at risk up to 50 million people in sub\u2010<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>aharan <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>frica. Current drug therapies are limited by toxicity and difficult treatment regimes and as the development of vaccines remains unlikely, the identification of better drugs to control this deadly disease is needed. Strategies for the identification of new lead compounds include phenotypic screening or target\u2010based approaches. Implementation of the latter has been hampered by the lack of defined targets that are both essential and druggable. In this issue of <jats:italic><jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>olecular <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>icrobiology<\/jats:italic>, <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>ones <jats:italic>et\u2009al<\/jats:italic>. (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#mmi12001-bib-1001\"\/>) report on the characterization of <jats:italic>T.\u2009brucei<\/jats:italic> pyridoxal kinase (<jats:styled-content style=\"fixed-case\">PdxK<\/jats:styled-content>), an enzyme required for the salvage of vitamin <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>6, an essential enzymatic cofactor. Genetic knock\u2010down and small molecule inhibitor studies were used to demonstrate that <jats:styled-content style=\"fixed-case\">PdxK<\/jats:styled-content> is essential for parasite growth both <jats:italic>in vitro<\/jats:italic> and in a mouse model, providing both genetic and chemical validation of the target. An enzyme assay compatible with high\u2010throughput screening (<jats:styled-content style=\"fixed-case\">HTS<\/jats:styled-content>) was developed and the <jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>\u2010ray crystal structure solved, showing the potential for species selective inhibition. These studies add a greatly needed additional target into the drug discovery pipeline for this deadly parasitic infection.<\/jats:p>","DOI":"10.1111\/mmi.12001","type":"journal-article","created":{"date-parts":[[2012,8,28]],"date-time":"2012-08-28T07:21:09Z","timestamp":1346138469000},"page":"10-14","source":"Crossref","is-referenced-by-count":18,"title":["Stoking the drug target pipeline for human <scp>A<\/scp>frican trypanosomiasis"],"prefix":"10.1111","volume":"86","author":[{"given":"Margaret A.","family":"Phillips","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Texas Southwestern Medical Center at Dallas  6001 Forest Park Rd Dallas TX 75390\u20109041 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,28]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2684"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.115089.110"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10771"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e32833f9fd0"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707354"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112642"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60829-1"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.11.44"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182010001137"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802611795429194"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.11.91"},{"key":"e_1_2_3_13_1","first-page":"175","article-title":"Drug discovery and development for neglected diseases: the DNDi model","volume":"5","author":"Chatelain E.","year":"2011","journal-title":"Drug Des Dev Ther"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802612799362977"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm200592f"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.230847"},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802611795429167"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001151"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2012.08189.x"},{"key":"e_1_2_3_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00246-11"},{"key":"e_1_2_3_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21429"},{"key":"e_1_2_3_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.05114-11"},{"key":"e_1_2_3_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00642-07"},{"key":"e_1_2_3_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2779"},{"key":"e_1_2_3_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr1053"},{"key":"e_1_2_3_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2012.05.001"},{"key":"e_1_2_3_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.212613"},{"key":"e_1_2_3_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152610791163336"},{"key":"e_1_2_3_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2011.05.006"},{"key":"e_1_2_3_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33945"},{"key":"e_1_2_3_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2011.04.005"},{"key":"e_1_2_3_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711014105"},{"key":"e_1_2_3_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(99)00002-X"},{"key":"e_1_2_3_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003326"},{"key":"e_1_2_3_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000720"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fmmi.12001","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mmi.12001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T12:14:15Z","timestamp":1695471255000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/mmi.12001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,28]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1111\/mmi.12001"],"URL":"https:\/\/doi.org\/10.1111\/mmi.12001","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,28]]}}}