{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T13:55:55Z","timestamp":1793109355779,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0009991","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000}}],"reference-count":159,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["501584"],"award-info":[{"award-number":["501584"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["5003009"],"award-info":[{"award-number":["5003009"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Soil transmitted helminths (STHs) are major human pathogens that infect over a billion people. Resistance to current anthelmintics is rising and new drugs are needed. Here we combine multiple approaches to find druggable targets in the anaerobic metabolic pathways STHs need to survive in their mammalian host. These require rhodoquinone (RQ), an electron carrier used by STHs and not their hosts. We identified 25 genes predicted to act in RQ-dependent metabolism including sensing hypoxia and RQ synthesis and found 9 are required. Since all 9 have mammalian orthologues, we used comparative genomics and structural modeling to identify those with active sites that differ between host and parasite. Together, we found 4 genes that are required for RQ-dependent metabolism and have different active sites. Finding these high confidence targets can open up<jats:italic>in silico<\/jats:italic>screens to identify species selective inhibitors of these enzymes as new anthelmintics.<\/jats:p>","DOI":"10.1371\/journal.pntd.0009991","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T18:52:18Z","timestamp":1638211938000},"page":"e0009991","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Identification of enzymes that have helminth-specific active sites and are required for Rhodoquinone-dependent metabolism as targets for new anthelmintics"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8503-9603","authenticated-orcid":true,"given":"Margot J.","family":"Lautens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6597-3952","authenticated-orcid":true,"given":"June H.","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7611-5400","authenticated-orcid":true,"given":"X\u00e8nia","family":"Serrat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0117-0592","authenticated-orcid":true,"given":"Samantha","family":"Del Borrello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Schertzberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9939-6014","authenticated-orcid":true,"given":"Andrew G.","family":"Fraser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"pntd.0009991.ref001","first-page":"394","article-title":"Effect of antiparasitic treatment in beef replacement heifers","volume":"33","author":"SW Bauck","year":"1992","journal-title":"Can Vet J"},{"key":"pntd.0009991.ref002","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.pt.2014.04.009","article-title":"Chasing helminths and their economic impact on farmed ruminants","volume":"30","author":"J Charlier","year":"2014","journal-title":"Trends Parasitol"},{"key":"pntd.0009991.ref003","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1756-3305-7-37","article-title":"Global numbers of infection and disease burden of soil transmitted helminth infections in 2010","volume":"7","author":"RL Pullan","year":"2014","journal-title":"Parasit Vectors"},{"key":"pntd.0009991.ref004","unstructured":"World Health Organization. Prevention and control of schistosomiasis and soil-transmitted helminthiasis: report of a WHO expert committee. 2002."},{"key":"pntd.0009991.ref005","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.6308762","article-title":"Ivermectin: a potent new antiparasitic agent","volume":"221","author":"WC Campbell","year":"1983","journal-title":"Science"},{"key":"pntd.0009991.ref006","doi-asserted-by":"crossref","first-page":"853","DOI":"10.2174\/138920112800399095","article-title":"History of avermectin and ivermectin, with notes on the history of other macrocyclic lactone antiparasitic agents","volume":"13","author":"WC Campbell","year":"2012","journal-title":"Curr Pharm Biotechnol"},{"key":"pntd.0009991.ref007","first-page":"347","article-title":"The levamisole story","volume":"20","author":"PA Janssen","year":"1976","journal-title":"Prog Drug Res Fortschritte Arzneimittelforschung Progres Rech Pharm"},{"key":"pntd.0009991.ref008","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1021\/ja01472a028","article-title":"Hydroboration. IX. The Hydroboration of Cyclic and Bicyclic Olefins\u2014Stereochemistry of the Hydroboration Reaction","volume":"83","author":"HC Brown","year":"1961","journal-title":"J Am Chem Soc"},{"key":"pntd.0009991.ref009","unstructured":"WHO model list of essential medicines. Jun 2019 [cited 16 Mar 2021]. https:\/\/www.who.int\/publications\/i\/item\/WHOMVPEMPIAU2019.06"},{"key":"pntd.0009991.ref010","first-page":"203","volume-title":"Advances in Parasitology","author":"HMPD Herath","year":"2021"},{"key":"pntd.0009991.ref011","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.vetpar.2011.11.048","article-title":"An inconvenient truth: Global worming and anthelmintic resistance","volume":"186","author":"RM Kaplan","year":"2012","journal-title":"Vet Parasitol"},{"key":"pntd.0009991.ref012","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.pt.2018.05.001","article-title":"Ten Events That Defined Anthelmintic Resistance Research","volume":"34","author":"NC Sangster","year":"2018","journal-title":"Trends Parasitol"},{"key":"pntd.0009991.ref013","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.pt.2004.07.010","article-title":"Drug resistance in veterinary helminths","volume":"20","author":"AJ Wolstenholme","year":"2004","journal-title":"Trends Parasitol"},{"key":"pntd.0009991.ref014","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1046\/j.1365-3156.2001.00774.x","article-title":"Anthelmintic resistance in human helminths: a review","volume":"6","author":"S Geerts","year":"2001","journal-title":"Trop Med Int Health"},{"key":"pntd.0009991.ref015","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ijpddr.2020.11.005","article-title":"Challenges and opportunities for the adoption of molecular diagnostics for anthelmintic resistance","volume":"14","author":"AC Kotze","year":"2020","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"pntd.0009991.ref016","first-page":"91","volume-title":"Advances in Parasitology","author":"W Moser","year":"2019"},{"key":"pntd.0009991.ref017","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.2174\/0929867033456549","article-title":"Parasite Mitochondria as Drug Target: Diversity and Dynamic Changes During the Life Cycle","volume":"10","author":"K Kita","year":"2003","journal-title":"Curr Med Chem"},{"key":"pntd.0009991.ref018","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0166-6851(88)90060-6","article-title":"Rhodoquinone requirement of the Hymenolepis diminuta mitochondrial electron transport system","volume":"28","author":"CF Fioravanti","year":"1988","journal-title":"Mol Biochem Parasitol"},{"key":"pntd.0009991.ref019","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1021\/ja01084a065","article-title":"Coenzyme Q. LXII. Structure and Synthesis of Rhodoquinone, a Natural Aminoquinone of the Coenzyme Q Group","volume":"87","author":"HW Moore","year":"1965","journal-title":"J Am Chem Soc"},{"key":"pntd.0009991.ref020","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/S0006-291X(72)80178-5","article-title":"Rhodoquinone specificity in the reactivation of succinoxidase activity of acetone-extracted Ascaris mitochondria","volume":"46","author":"M Sato","year":"1972","journal-title":"Biochem Biophys Res Commun"},{"key":"pntd.0009991.ref021","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1093\/oxfordjournals.jbchem.a129090","article-title":"Occurrence of ubiquinone and rhodoquinone in parasitic nematodes, metastrongylus elongatus and Ascaris lumbricoides var. suis","volume":"65","author":"M Sato","year":"1969","journal-title":"J Biochem (Tokyo)"},{"key":"pntd.0009991.ref022","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/0169-4758(94)90245-3","article-title":"Energy generation in parasitic helminths","volume":"10","author":"AGM Tielens","year":"1994","journal-title":"Parasitol Today"},{"key":"pntd.0009991.ref023","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0005-2728(98)00045-0","article-title":"The electron transport chain in anaerobically functioning eukaryotes","volume":"1365","author":"AGM Tielens","year":"1998","journal-title":"Biochim Biophys Acta\u2014Bioenerg"},{"key":"pntd.0009991.ref024","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1128\/MMBR.05024-11","article-title":"Biochemistry and evolution of anaerobic energy metabolism in eukaryotes","volume":"76","author":"M M\u00fcller","year":"2012","journal-title":"Microbiol Mol Biol Rev MMBR"},{"key":"pntd.0009991.ref025","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1098\/rstb.2002.1182","article-title":"Biochemical and evolutionary aspects of anaerobically functioning mitochondria","volume":"358","author":"JJ van Hellemond","year":"2003","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"pntd.0009991.ref026","doi-asserted-by":"crossref","first-page":"31065","DOI":"10.1074\/jbc.270.52.31065","article-title":"Rhodoquinone and complex II of the electron transport chain in anaerobically functioning eukaryotes","volume":"270","author":"JJ Van Hellemond","year":"1995","journal-title":"J Biol Chem"},{"key":"pntd.0009991.ref027","doi-asserted-by":"crossref","first-page":"148278","DOI":"10.1016\/j.bbabio.2020.148278","article-title":"Rhodoquinone in bacteria and animals: Two distinct pathways for biosynthesis of this key electron transporter used in anaerobic bioenergetics","volume":"1861","author":"G Salinas","year":"2020","journal-title":"Biochim Biophys Acta BBA\u2014Bioenerg"},{"key":"pntd.0009991.ref028","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.parint.2007.08.002","article-title":"Change of subunit composition of mitochondrial complex II (succinate\u2013ubiquinone reductase\/quinol\u2013fumarate reductase) in Ascaris suum during the migration in the experimental host","volume":"57","author":"F Iwata","year":"2008","journal-title":"Parasitol Int"},{"key":"pntd.0009991.ref029","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0166-6851(94)90154-6","article-title":"Differential expression of two succinate dehydrogenase subunit-B genes and a transition in energy metabolism during the development of the parasitic nematode Haemonchus contortus","volume":"66","author":"MH Roos","year":"1994","journal-title":"Mol Biochem Parasitol"},{"key":"pntd.0009991.ref030","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1074\/jbc.270.2.928","article-title":"Stage-specific Isoforms of Complex II (Succinate-Ubiquinone Oxidoreductase) in Mitochondria from the Parasitic Nematode, Ascaris suum(*)","volume":"270","author":"S Takamiya","year":"1995","journal-title":"J Biol Chem"},{"key":"pntd.0009991.ref031","doi-asserted-by":"crossref","first-page":"7485","DOI":"10.1038\/ncomms8485","article-title":"Caenorhabditis elegans is a useful model for anthelmintic discovery","volume":"6","author":"AR Burns","year":"2015","journal-title":"Nat Commun"},{"key":"pntd.0009991.ref032","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0005-2728(01)00237-7","article-title":"Role of complex II in anaerobic respiration of the parasite mitochondria from Ascaris suum and Plasmodium falciparum","volume":"1553","author":"K Kita","year":"2002","journal-title":"Biochim Biophys Acta BBA\u2014Bioenerg"},{"key":"pntd.0009991.ref033","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2019.01043","article-title":"Complex I and II Subunit Gene Duplications Provide Increased Fitness to Worms","volume":"10","author":"L Otero","year":"2019","journal-title":"Front Genet"},{"key":"pntd.0009991.ref034","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.48165","article-title":"Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway","volume":"8","author":"S Del Borrello","year":"2019","journal-title":"eLife"},{"key":"pntd.0009991.ref035","doi-asserted-by":"crossref","first-page":"e56376","DOI":"10.7554\/eLife.56376","article-title":"Alternative splicing of coq-2 controls the levels of rhodoquinone in animals","volume":"9","author":"JH Tan","year":"2020","journal-title":"eLife"},{"key":"pntd.0009991.ref036","unstructured":"OpenTreeOfLife, Redelings B, Reyes LLS, Cranston KA, Allman J, Holder MT, et al. Open Tree of Life Synthetic Tree. 2019 [cited 5 Sep 2021]."},{"key":"pntd.0009991.ref037","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1534\/g3.118.200374","article-title":"Acute Effects of Drugs on Caenorhabditis elegans Movement Reveal Complex Responses and Plasticity","volume":"8","author":"M Spensley","year":"2018","journal-title":"G3 Bethesda Md"},{"key":"pntd.0009991.ref038","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1073\/pnas.0908044107","article-title":"Protein interactions and ligand binding: from protein subfamilies to functional specificity","volume":"107","author":"A Rausell","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pntd.0009991.ref039","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/B978-012473345-9\/50005-2","volume-title":"Biochemistry and Molecular Biology of Parasites","author":"R Komuniecki","year":"1995"},{"key":"pntd.0009991.ref040","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0166-6851(96)02738-7","article-title":"Rhodoquinone is synthesized de novo by Fasciola hepatica","volume":"82","author":"JJ Van Hellemond","year":"1996","journal-title":"Mol Biochem Parasitol"},{"key":"pntd.0009991.ref041","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.biochi.2019.01.006","article-title":"Structural basis for the design of selective inhibitors for Schistosoma mansoni dihydroorotate dehydrogenase","volume":"158","author":"MC Nonato","year":"2019","journal-title":"Biochimie"},{"key":"pntd.0009991.ref042","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bbabio.2003.10.006","article-title":"Rhodoquinone reaction site of mitochondrial complex I, in parasitic helminth, Ascaris suum","volume":"1608","author":"T Yamashita","year":"2004","journal-title":"Biochim Biophys Acta\u2014Bioenerg"},{"key":"pntd.0009991.ref043","doi-asserted-by":"crossref","first-page":"4587","DOI":"10.1093\/nar\/gkp425","article-title":"An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia","volume":"37","author":"Y Benita","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"pntd.0009991.ref044","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0092-8674(01)00507-4","article-title":"C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation","volume":"107","author":"ACR Epstein","year":"2001","journal-title":"Cell"},{"key":"pntd.0009991.ref045","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1016\/j.cub.2010.10.057","article-title":"Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity","volume":"20","author":"S-JJ Lee","year":"2010","journal-title":"Curr Biol"},{"key":"pntd.0009991.ref046","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.tem.2010.02.006","article-title":"Hypoxia signaling and resistance in C. elegans","volume":"21","author":"JA Powell-Coffman","year":"2010","journal-title":"Trends Endocrinol Metab"},{"key":"pntd.0009991.ref047","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1534\/genetics.106.063594","article-title":"The Caenorhabditis elegans rhy-1 gene inhibits HIF-1 hypoxia-inducible factor activity in a negative feedback loop that does not include vhl-1","volume":"174","author":"C Shen","year":"2006","journal-title":"Genetics"},{"key":"pntd.0009991.ref048","doi-asserted-by":"crossref","first-page":"20580","DOI":"10.1074\/jbc.M501894200","article-title":"Roles of the HIF-1 hypoxia-inducible factor during hypoxia response in Caenorhabditis elegans","volume":"280","author":"C Shen","year":"2005","journal-title":"J Biol Chem"},{"key":"pntd.0009991.ref049","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1534\/genetics.109.107284","article-title":"Two Distinct Roles for EGL-9 in the Regulation of HIF-1-Mediated Gene Expression in Caenorhabditis elegans","volume":"183","author":"Z Shao","year":"2009","journal-title":"Genetics"},{"key":"pntd.0009991.ref050","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.0020289","article-title":"Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans","volume":"2","author":"T Bishop","year":"2004","journal-title":"PLoS Biol"},{"key":"pntd.0009991.ref051","doi-asserted-by":"crossref","first-page":"e1000486","DOI":"10.1371\/journal.pgen.1000486","article-title":"HIF-1 modulates dietary restriction-mediated lifespan extension via IRE-1 in Caenorhabditis elegans","volume":"5","author":"D Chen","year":"2009","journal-title":"PLoS Genet"},{"key":"pntd.0009991.ref052","doi-asserted-by":"crossref","first-page":"5033","DOI":"10.1128\/MCB.00922-10","article-title":"Protein Misfolding Induces Hypoxic Preconditioning via a Subset of the Unfolded Protein Response Machinery","volume":"30","author":"XR Mao","year":"2010","journal-title":"Mol Cell Biol"},{"key":"pntd.0009991.ref053","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1006\/dbio.1999.9470","article-title":"Expression and Function of Members of a Divergent Nuclear Receptor Family in Caenorhabditis elegans","volume":"215","author":"T Miyabayashi","year":"1999","journal-title":"Dev Biol"},{"key":"pntd.0009991.ref054","doi-asserted-by":"crossref","first-page":"e16790","DOI":"10.1371\/journal.pone.0016790","article-title":"Environmental and Genetic Preconditioning for Long-Term Anoxia Responses Requires AMPK in Caenorhabditis elegans","volume":"6","author":"BL LaRue","year":"2011","journal-title":"PLOS ONE"},{"key":"pntd.0009991.ref055","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1534\/genetics.106.061390","article-title":"Glyceraldehyde-3-Phosphate Dehydrogenase Mediates Anoxia Response and Survival in Caenorhabditis elegans","volume":"174","author":"AR Mendenhall","year":"2006","journal-title":"Genetics"},{"key":"pntd.0009991.ref056","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1126\/science.1168532","article-title":"Protection of C. elegans from Anoxia by HYL-2 Ceramide Synthase","volume":"324","author":"V Menuz","year":"2009","journal-title":"Science"},{"key":"pntd.0009991.ref057","doi-asserted-by":"crossref","first-page":"e0159989","DOI":"10.1371\/journal.pone.0159989","article-title":"The Mitochondrial Unfolded Protein Response Protects against Anoxia in Caenorhabditis elegans","volume":"11","author":"S Pe\u00f1a","year":"2016","journal-title":"PLOS ONE"},{"key":"pntd.0009991.ref058","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1242\/jeb.203.16.2467","article-title":"Broad oxygen tolerance in the nematode Caenorhabditis elegans","volume":"203","author":"WAV Voorhies","year":"2000","journal-title":"J Exp Biol"},{"key":"pntd.0009991.ref059","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1091\/mbc.01-12-0594","article-title":"Dephosphorylation of Cell Cycle\u2013regulated Proteins Correlates with Anoxia-induced Suspended Animation in Caenorhabditis elegans","volume":"13","author":"PA Padilla","year":"2002","journal-title":"Mol Biol Cell"},{"key":"pntd.0009991.ref060","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1534\/g3.112.003830","article-title":"Large-Scale Screening for Targeted Knockouts in the Caenorhabditis elegans Genome","volume":"2","author":"The C. elegans Deletion Mutant Consortium","year":"2012","journal-title":"G3 GenesGenomesGenetics"},{"key":"pntd.0009991.ref061","first-page":"611","article-title":"Inhibition of germline proliferation during C. elegans dauer development requires PTEN, LKB1 and AMPK signalling","volume":"133","author":"P Narbonne","year":"2006","journal-title":"Dev Camb Engl"},{"key":"pntd.0009991.ref062","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1101\/gad.1775409","article-title":"Rictor\/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans","volume":"23","author":"AA Soukas","year":"2009","journal-title":"Genes Dev"},{"key":"pntd.0009991.ref063","doi-asserted-by":"crossref","first-page":"e1000060","DOI":"10.1371\/journal.pbio.1000060","article-title":"Rictor\/TORC2 Regulates Caenorhabditis elegans Fat Storage, Body Size, and Development through sgk-1","volume":"7","author":"KT Jones","year":"2009","journal-title":"PLOS Biol"},{"key":"pntd.0009991.ref064","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1895\/wormbook.1.146.1","article-title":"Intermediary metabolism","author":"BP Braeckman","year":"2009","journal-title":"WormBook"},{"key":"pntd.0009991.ref065","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0014-5793(03)00560-X","article-title":"Management of cellular energy by the AMP-activated protein kinase system","volume":"546","author":"DG Hardie","year":"2003","journal-title":"FEBS Lett"},{"key":"pntd.0009991.ref066","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1101\/gad.1255404","article-title":"The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans","volume":"18","author":"J Apfeld","year":"2004","journal-title":"Genes Dev"},{"key":"pntd.0009991.ref067","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/nature07536","article-title":"Caenorhabditis elegans dauers need LKB1\/AMPK to ration lipid reserves and ensure long-term survival","volume":"457","author":"P Narbonne","year":"2009","journal-title":"Nature"},{"key":"pntd.0009991.ref068","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1534\/genetics.119.302504","article-title":"TOR Signaling in Caenorhabditis elegans Development, Metabolism, and Aging","volume":"213","author":"TK Blackwell","year":"2019","journal-title":"Genetics"},{"key":"pntd.0009991.ref069","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1017\/S0016672300027099","article-title":"Genetic analysis of a large autosomal region in Caenorhabditis elegans by the use of a free duplication","volume":"49","author":"AM Howell","year":"1987","journal-title":"Genet Res"},{"key":"pntd.0009991.ref070","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/S0960-9822(02)01091-6","article-title":"TOR Deficiency in C. elegans Causes Developmental Arrest and Intestinal Atrophy by Inhibition of mRNA Translation","volume":"12","author":"X Long","year":"2002","journal-title":"Curr Biol"},{"key":"pntd.0009991.ref071","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S1534-5807(04)00095-4","article-title":"C. elegans SGK-1 Is the Critical Component in the Akt\/PKB Kinase Complex to Control Stress Response and Life Span","volume":"6","author":"M Hertweck","year":"2004","journal-title":"Dev Cell"},{"key":"pntd.0009991.ref072","doi-asserted-by":"crossref","first-page":"e107671","DOI":"10.1371\/journal.pone.0107671","article-title":"Prohibitin-Mediated Lifespan and Mitochondrial Stress Implicate SGK-1, Insulin\/IGF and mTORC2 in C. elegans","volume":"9","author":"R Gatsi","year":"2014","journal-title":"PLOS ONE"},{"key":"pntd.0009991.ref073","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1111\/acel.12120","article-title":"Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16\/FoxO regulation","volume":"12","author":"AT-Y Chen","year":"2013","journal-title":"Aging Cell"},{"key":"pntd.0009991.ref074","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/j.celrep.2019.09.072","article-title":"Mitochondrial Perturbations Couple mTORC2 to Autophagy in C. elegans","volume":"29","author":"H Aspernig","year":"2019","journal-title":"Cell Rep"},{"key":"pntd.0009991.ref075","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.cell.2008.01.030","article-title":"Direct Inhibition of the Longevity-Promoting Factor SKN-1 by Insulin-like Signaling in C. elegans","volume":"132","author":"JMA Tullet","year":"2008","journal-title":"Cell"},{"key":"pntd.0009991.ref076","doi-asserted-by":"crossref","first-page":"4441","DOI":"10.1016\/j.bmcl.2009.05.051","article-title":"Design and synthesis of orally bioavailable serum and glucocorticoid-regulated kinase 1 (SGK1) inhibitors","volume":"19","author":"M Hammond","year":"2009","journal-title":"Bioorg Med Chem Lett"},{"key":"pntd.0009991.ref077","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1110\/ps.073161707","article-title":"Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP\u2013PNP","volume":"16","author":"B Zhao","year":"2007","journal-title":"Protein Sci Publ Protein Soc"},{"key":"pntd.0009991.ref078","doi-asserted-by":"crossref","first-page":"11047","DOI":"10.1074\/jbc.AC119.009475","article-title":"The kynurenine pathway is essential for rhodoquinone biosynthesis in Caenorhabditis elegans","volume":"294","author":"PM Roberts Buceta","year":"2019","journal-title":"J Biol Chem"},{"key":"pntd.0009991.ref079","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0021-9258(18)55759-8","article-title":"The metabolism of D- and L-tryptophan and D- and L-kynurenine by liver and brain preparations","volume":"195","author":"Mason Merle","year":"1952","journal-title":"J Biol Chem"},{"key":"pntd.0009991.ref080","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1093\/oxfordjournals.jbchem.a133087","article-title":"Purification and Properties of Kynureninase from Rat Liver","volume":"88","author":"F Takeuchi","year":"1980","journal-title":"J Biochem (Tokyo)"},{"key":"pntd.0009991.ref081","first-page":"889","article-title":"Studies on oxygenases; enzymatic formation of kynurenine from tryptophan","volume":"229","author":"O Hayaishi","year":"1957","journal-title":"J Biol Chem"},{"key":"pntd.0009991.ref082","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0021-9258(18)57277-X","article-title":"Concerning the mechanism of the mammalian conversion of tryptophan into kynurenine, kynurenic acid, and nicotinic acid","volume":"175","author":"C Heidelberger","year":"1948","journal-title":"J Biol Chem"},{"key":"pntd.0009991.ref083","first-page":"139","article-title":"Studies on the intermediary metabolism of tryptophane. On kynurenine, an intermediary product of the metabolism of tryptophane","volume":"195","author":"Y Kotake","year":"1931","journal-title":"Hoppe Seylers Z Physiol Chem"},{"key":"pntd.0009991.ref084","doi-asserted-by":"crossref","first-page":"39199","DOI":"10.1038\/srep39199","article-title":"Identification of an evolutionary conserved structural loop that is required for the enzymatic and biological function of tryptophan 2,3-dioxygenase","volume":"6","author":"H Michels","year":"2016","journal-title":"Sci Rep"},{"key":"pntd.0009991.ref085","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014a visualization system for exploratory research and analysis","volume":"25","author":"EF Pettersen","year":"2004","journal-title":"J Comput Chem"},{"key":"pntd.0009991.ref086","doi-asserted-by":"crossref","first-page":"5320","DOI":"10.1021\/jm2006782","article-title":"Tryptophan 2,3-Dioxygenase (TDO) Inhibitors. 3-(2-(Pyridyl)ethenyl)indoles as Potential Anticancer Immunomodulators","volume":"54","author":"E Dolu\u0161i\u0107","year":"2011","journal-title":"J Med Chem"},{"key":"pntd.0009991.ref087","doi-asserted-by":"crossref","first-page":"35169","DOI":"10.1038\/srep35169","article-title":"Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase","volume":"6","author":"A Lewis-Ballester","year":"2016","journal-title":"Sci Rep"},{"key":"pntd.0009991.ref088","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1006\/abbi.1999.1465","article-title":"Free-Living Nematodes Caenorhabditis elegans Possess in Their Mitochondria an Additional Rhodoquinone, an Essential Component of the Eukaryotic Fumarate Reductase System","volume":"371","author":"S Takamiya","year":"2002","journal-title":"Arch Biochem Biophys"},{"key":"pntd.0009991.ref089","doi-asserted-by":"crossref","first-page":"16212","DOI":"10.1073\/pnas.0604567103","article-title":"Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool","volume":"103","author":"J Zhang","year":"2006","journal-title":"Proc Natl Acad Sci"},{"key":"pntd.0009991.ref090","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1107\/S1744309109031352","article-title":"Crystallization of mitochondrial rhodoquinol-fumarate reductase from the parasitic nematode Ascaris suum with the specific inhibitor flutolanil","volume":"65","author":"A Osanai","year":"2009","journal-title":"Acta Crystallograph Sect F Struct Biol Cryst Commun"},{"key":"pntd.0009991.ref091","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0169-4758(92)90009-Q","article-title":"Electron-transfer complexes of mitochondria in Ascaris suum","volume":"8","author":"K. Kita","year":"1992","journal-title":"Parasitol Today"},{"key":"pntd.0009991.ref092","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/S0021-9258(18)64408-4","article-title":"Succinic and reduced diphosphopyridine nucleotide oxidase systems of Ascaris muscle","volume":"236","author":"E Kmetec","year":"1961","journal-title":"J Biol Chem"},{"key":"pntd.0009991.ref093","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/j.1748-1716.1909.tb00079.x","article-title":"Studien \u00fcber die Beeinflussung des Gasaustausches des \u00fcberlebenden Froschmuskels durch verschiedene Stoffe","volume":"22","author":"T. Thunberg","year":"1909","journal-title":"Skand Arch F\u00fcr Physiol"},{"key":"pntd.0009991.ref094","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1021\/bi00336a016","article-title":"Electron transfer flavoprotein-ubiquinone oxidoreductase from pig liver: purification and molecular, redox, and catalytic properties","volume":"24","author":"JD Beckmann","year":"1985","journal-title":"Biochemistry"},{"key":"pntd.0009991.ref095","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0005-2728(89)80210-5","article-title":"Electron-transfer flavoprotein from anaerobic Ascaris suum mitochondria and its role in NADH-dependent 2-methyl branched-chain enoyl-CoA reduction","volume":"975","author":"R Komuniecki","year":"1989","journal-title":"BBA\u2014Bioenerg"},{"key":"pntd.0009991.ref096","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/0006-291X(75)90555-0","article-title":"A new membrane iron-sulfur flavoprotein of the mitochondrial electron transfer system the entrance point of the fatty acyl dehydrogenation pathway?","volume":"66","author":"FJ Ruzicka","year":"1975","journal-title":"Biochem Biophys Res Commun"},{"key":"pntd.0009991.ref097","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1432-1033.1983.tb07533.x","article-title":"Proline Dehydrogenase from Escherichia coli K12","volume":"134","author":"JLA Abrahamson","year":"1983","journal-title":"Eur J Biochem"},{"key":"pntd.0009991.ref098","doi-asserted-by":"crossref","first-page":"574","DOI":"10.2307\/3278709","article-title":"Proline in Fascioliasis: I. Comparative Activities of Ornithine-\u03b4-Transaminase and Proline Oxidase in Fasciola and in Mammalian Livers","volume":"60","author":"J Ertel","year":"1974","journal-title":"J Parasitol"},{"key":"pntd.0009991.ref099","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1104\/pp.53.3.440","article-title":"Nicotinamide Adenine Dinucleotide-dependent Proline Dehydrogenase in Chlorella","volume":"53","author":"AD McNamer","year":"1974","journal-title":"Plant Physiol"},{"key":"pntd.0009991.ref100","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1042\/bj0300629","article-title":"\u03b1-Glycerophosphate dehydrogenase","volume":"30","author":"DE Green","year":"1936","journal-title":"Biochem J"},{"key":"pntd.0009991.ref101","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.bbabio.2012.11.014","article-title":"The function and the role of the mitochondrial glycerol-3-phosphate dehydrogenase in mammalian tissues","volume":"1827","author":"T Mr\u00e1\u010dek","year":"2013","journal-title":"Biochim Biophys Acta BBA\u2014Bioenerg"},{"key":"pntd.0009991.ref102","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/0014-4894(76)90106-5","article-title":"Schistosomatium douthitti: Carbohydrate metabolism in the adults","volume":"40","author":"SH Rogers","year":"1976","journal-title":"Exp Parasitol"},{"key":"pntd.0009991.ref103","article-title":"Mammalian dihydroorotate\u2014ubiquinone reductase complex","author":"RW Miller","year":"1968","journal-title":"Can J Biochem"},{"key":"pntd.0009991.ref104","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1534\/genetics.111.129841","article-title":"The response of caenorhabditis elegans to Hydrogen Sulfide and Hydrogen Cyanide","volume":"189","author":"MW Budde","year":"2011","journal-title":"Genetics"},{"key":"pntd.0009991.ref105","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1042\/BJ20031933","article-title":"Identification of a dehydrogenase acting on D-2-hydroxyglutarate","volume":"381","author":"Y Achouri","year":"2004","journal-title":"Biochem J"},{"key":"pntd.0009991.ref106","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s10545-012-9462-5","article-title":"Progress in understanding 2-hydroxyglutaric acidurias","volume":"35","author":"M Kranendijk","year":"2012","journal-title":"J Inherit Metab Dis"},{"key":"pntd.0009991.ref107","doi-asserted-by":"crossref","first-page":"7768","DOI":"10.1038\/ncomms8768","article-title":"D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2","volume":"6","author":"A-P Lin","year":"2015","journal-title":"Nat Commun"},{"key":"pntd.0009991.ref108","doi-asserted-by":"crossref","first-page":"3922","DOI":"10.1021\/bi00336a017","article-title":"Reaction of electron-transfer flavoprotein with electron transfer flavoprotein-ubiquinone oxidoreductase","volume":"24","author":"JD Beckmann","year":"1985","journal-title":"Biochemistry"},{"key":"pntd.0009991.ref109","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1042\/bj2410883","article-title":"Reactions of electron-transfer flavoprotein and electron-transfer flavoprotein: ubiquinone oxidoreductase","volume":"241","author":"RR Ramsay","year":"1987","journal-title":"Biochem J"},{"key":"pntd.0009991.ref110","doi-asserted-by":"crossref","first-page":"20360","DOI":"10.1016\/S0021-9258(20)80736-4","article-title":"Purification and characterization of electron-transfer flavoprotein:rhodoquinone oxidoreductase from anaerobic mitochondria of the adult parasitic nematode, Ascaris suum","volume":"268","author":"YC Ma","year":"1993","journal-title":"J Biol Chem"},{"key":"pntd.0009991.ref111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0046140","article-title":"Profiling the Anaerobic Response of C. elegans Using GC-MS","volume":"7","author":"JA Butler","year":"2012","journal-title":"PLoS ONE"},{"key":"pntd.0009991.ref112","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.cels.2016.04.012","article-title":"A Caenorhabditis elegans Genome-Scale Metabolic Network Model","volume":"2","author":"LS Yilmaz","year":"2016","journal-title":"Cell Syst"},{"key":"pntd.0009991.ref113","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1016\/S0021-9258(18)69856-4","article-title":"The mechanism of formation of succinate and propionate by Ascaris lumbricoides muscle","volume":"234","author":"HJ Saz","year":"1959","journal-title":"J Biol Chem"},{"key":"pntd.0009991.ref114","first-page":"257","article-title":"Malate dehydrogenases\u2014structure and function","volume":"21","author":"P Min\u00e1rik","year":"2002","journal-title":"Gen Physiol Biophys"},{"key":"pntd.0009991.ref115","doi-asserted-by":"crossref","first-page":"e20085","DOI":"10.1371\/journal.pone.0020085","article-title":"OrthoList: a compendium of C. elegans genes with human orthologs","volume":"6","author":"DD Shaye","year":"2011","journal-title":"PloS One"},{"key":"pntd.0009991.ref116","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3109\/10425170109047568","article-title":"Characterization of a cadmium-inducible isoform of pyruvate carboxylase from Caenorhabditis elegans","volume":"12","author":"VH Liao","year":"2001","journal-title":"DNA Seq J DNA Seq Mapp"},{"key":"pntd.0009991.ref117","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1741-7007-8-14","article-title":"A metabolic signature of long life in Caenorhabditis elegans","volume":"8","author":"S Fuchs","year":"2010","journal-title":"BMC Biol"},{"key":"pntd.0009991.ref118","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.mad.2006.01.006","article-title":"Diapause-associated metabolic traits reiterated in long-lived daf-2 mutants in the nematode Caenorhabditis elegans","volume":"127","author":"JJ McElwee","year":"2006","journal-title":"Mech Ageing Dev"},{"key":"pntd.0009991.ref119","doi-asserted-by":"crossref","DOI":"10.1093\/ve\/vey016","article-title":"Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10","volume":"4","author":"MA Suchard","year":"2018","journal-title":"Virus Evol"},{"key":"pntd.0009991.ref120","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/B978-012473346-6\/50017-X","volume-title":"Molecular Medical Parasitology","author":"R Komuniecki","year":"2003"},{"key":"pntd.0009991.ref121","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1006\/dbio.1995.1156","article-title":"Bifunctional Glyoxylate Cycle Protein of Caenorhabditis elegans: A Developmentally Regulated Protein of Intestine and Muscle","volume":"169","author":"F Liu","year":"1995","journal-title":"Dev Biol"},{"key":"pntd.0009991.ref122","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0012-1606(89)90214-5","article-title":"Developmental regulation of energy metabolism in Caenorhabditis elegans","volume":"132","author":"WG Wadsworth","year":"1989","journal-title":"Dev Biol"},{"key":"pntd.0009991.ref123","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/0010-406X(70)90974-6","article-title":"The glyoxylate cycle and the conversion of triglycerides to carbohydrates in developing eggs of Ascaris lumbricoides","volume":"35","author":"J Barrett","year":"1970","journal-title":"Comp Biochem Physiol"},{"key":"pntd.0009991.ref124","article-title":"Changes in activity of certain enzymes of the tricarboxylic acid cycle and the glyoxylate cycle during the initiation of conidiation of Aspergillus niger","author":"JC Galbraith","year":"1969","journal-title":"Can J Microbiol"},{"key":"pntd.0009991.ref125","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/180035a0","article-title":"A Mechanism of Conversion of Fat to Carbohydrate in Castor Beans","volume":"180","author":"HL Kornberg","year":"1957","journal-title":"Nature"},{"key":"pntd.0009991.ref126","doi-asserted-by":"crossref","first-page":"9085","DOI":"10.1038\/s41598-019-45548-7","article-title":"Identification of small molecule enzyme inhibitors as broad-spectrum anthelmintics","volume":"9","author":"R Tyagi","year":"2019","journal-title":"Sci Rep"},{"key":"pntd.0009991.ref127","doi-asserted-by":"crossref","DOI":"10.3389\/fchem.2019.00920","article-title":"Rational Drug Design of Axl Tyrosine Kinase Type I Inhibitors as Promising Candidates Against Cancer","volume":"7","author":"E Sarukhanyan","year":"2020","journal-title":"Front Chem"},{"key":"pntd.0009991.ref128","first-page":"613","article-title":"Integrated In Silico-In Vitro Discovery of Lung Cancer-related Tumor Pyruvate Kinase M2 (PKM2) Inhibitors","volume":"12","author":"X Ye","year":"2016","journal-title":"Med Chem Shariqah United Arab Emir"},{"key":"pntd.0009991.ref129","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1645\/14-703.1","article-title":"Anthelmintic Drug Discovery: Into the Future","volume":"101","author":"TG Geary","year":"2015","journal-title":"J Parasitol"},{"key":"pntd.0009991.ref130","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/s41588-018-0262-1","article-title":"Comparative genomics of the major parasitic worms","volume":"51","author":"International Helminth Genomes Consortium","year":"2019","journal-title":"Nat Genet"},{"key":"pntd.0009991.ref131","first-page":"87","volume-title":"Advances in Parasitology","author":"RB Gasser","year":"2016"},{"key":"pntd.0009991.ref132","doi-asserted-by":"crossref","first-page":"e1001091","DOI":"10.1371\/journal.ppat.1001091","article-title":"Phylogenomics of Ligand-Gated Ion Channels Predicts Monepantel Effect","volume":"6","author":"L Rufener","year":"2010","journal-title":"PLOS Pathog"},{"key":"pntd.0009991.ref133","doi-asserted-by":"crossref","first-page":"5843","DOI":"10.1523\/JNEUROSCI.17-15-05843.1997","article-title":"Caenorhabditis elegans Levamisole Resistance Geneslev-1, unc-29, and unc-38 Encode Functional Nicotinic Acetylcholine Receptor Subunits","volume":"17","author":"JT Fleming","year":"1997","journal-title":"J Neurosci"},{"key":"pntd.0009991.ref134","first-page":"1","volume-title":"Reviews of Physiology, Biochemistry and Pharmacology","author":"RC Hogg","year":"2003"},{"key":"pntd.0009991.ref135","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0928-4257(98)80140-X","article-title":"Allosteric nicotinic receptors, human pathologies","volume":"92","author":"C L\u00e9na","year":"1998","journal-title":"J Physiol-Paris"},{"key":"pntd.0009991.ref136","doi-asserted-by":"crossref","first-page":"18590","DOI":"10.1073\/pnas.0806933105","article-title":"Eight genes are required for functional reconstitution of the Caenorhabditis elegans levamisole-sensitive acetylcholine receptor","volume":"105","author":"T Boulin","year":"2008","journal-title":"Proc Natl Acad Sci"},{"issue":"Suppl","key":"pntd.0009991.ref137","first-page":"S71","article-title":"Drug resistance and neurotransmitter receptors of nematodes: Recent studies on the mode of action of levamisole","volume":"131","author":"R Martin","year":"2005","journal-title":"Parasitology"},{"key":"pntd.0009991.ref138","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/BF01138170","article-title":"The fumarate reductase system as a site of anthelmintic attack in Ascaris suum","volume":"4","author":"MM Barrowman","year":"1984","journal-title":"Biosci Rep"},{"key":"pntd.0009991.ref139","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/BF00316579","article-title":"The effectiveness of N-acetylcysteine in isolated hepatocytes, against the toxicity of paracetamol, acrolein, and paraquat","volume":"55","author":"JR Dawson","year":"1984","journal-title":"Arch Toxicol"},{"key":"pntd.0009991.ref140","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1083\/jcb.109.6.2993","article-title":"Genetic and molecular analysis of a Caenorhabditis elegans beta-tubulin that conveys benzimidazole sensitivity","volume":"109","author":"M Driscoll","year":"1989","journal-title":"J Cell Biol"},{"key":"pntd.0009991.ref141","doi-asserted-by":"crossref","first-page":"e1007226","DOI":"10.1371\/journal.ppat.1007226","article-title":"Extreme allelic heterogeneity at a Caenorhabditis elegans beta-tubulin locus explains natural resistance to benzimidazoles","volume":"14","author":"SR Hahnel","year":"2018","journal-title":"PLOS Pathog"},{"key":"pntd.0009991.ref142","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/0169-4758(90)90227-U","article-title":"Mode of action of benzimidazoles","volume":"6","author":"E. Lacey","year":"1990","journal-title":"Parasitol Today"},{"key":"pntd.0009991.ref143","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1017\/S003118209700125X","article-title":"Schistosoma mansoni sporocysts contain rhodoquinone and produce succinate by fumarate reduction","volume":"115","author":"JJ Van Hellemond","year":"1997","journal-title":"Parasitology"},{"issue":"Pt 2","key":"pntd.0009991.ref144","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1042\/bj3040321","article-title":"Expression and functional properties of fumarate reductase","volume":"304","author":"JJ Van Hellemond","year":"1994","journal-title":"Biochem J"},{"key":"pntd.0009991.ref145","doi-asserted-by":"crossref","first-page":"15287","DOI":"10.3390\/ijms160715287","article-title":"Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria","volume":"16","author":"DK Inaoka","year":"2015","journal-title":"Int J Mol Sci"},{"key":"pntd.0009991.ref146","first-page":"1","article-title":"Maintenance of C. elegans","author":"T. Stiernagle","year":"2006","journal-title":"WormBook Online Rev C Elegans Biol"},{"key":"pntd.0009991.ref147","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/msb.2011.75","article-title":"Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega","volume":"7","author":"F Sievers","year":"2011","journal-title":"Mol Syst Biol"},{"key":"pntd.0009991.ref148","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1093\/bioinformatics\/btv494","article-title":"msa: an R package for multiple sequence alignment","volume":"31","author":"U Bodenhofer","year":"2015","journal-title":"Bioinformatics"},{"key":"pntd.0009991.ref149","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/molbev\/msz189","article-title":"ModelTest-NG: A New and Scalable Tool for the Selection of DNA and Protein Evolutionary Models","volume":"37","author":"D Darriba","year":"2020","journal-title":"Mol Biol Evol"},{"key":"pntd.0009991.ref150","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.jtbi.2008.04.005","article-title":"The conditioned reconstructed process","volume":"253","author":"T. Gernhard","year":"2008","journal-title":"J Theor Biol"},{"key":"pntd.0009991.ref151","first-page":"21","article-title":"A Mathematical Theory of Evolution, Based on the Conclusions of Dr. J. C. Willis, F.R.S","volume":"21","author":"GU Yule","year":"1925","journal-title":"Philos Trans R Soc Lond Ser B Contain Pap Biol Character"},{"key":"pntd.0009991.ref152","doi-asserted-by":"crossref","unstructured":"Miller MA, Pfeiffer W, Schwartz T. The CIPRES science gateway: a community resource for phylogenetic analyses. Proceedings of the 2011 TeraGrid Conference on Extreme Digital Discovery\u2014TG \u201811. Salt Lake City, Utah: ACM Press; 2011. p. 1.","DOI":"10.1145\/2016741.2016785"},{"key":"pntd.0009991.ref153","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1093\/sysbio\/syy032","article-title":"Posterior Summarization in Bayesian Phylogenetics Using Tracer 1.7","volume":"67","author":"A Rambaut","year":"2018","journal-title":"Syst Biol"},{"key":"pntd.0009991.ref154","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1093\/bioinformatics\/btr688","article-title":"JDet: interactive calculation and visualization of function-related conservation patterns in multiple sequence alignments and structures","volume":"28","author":"T Muth","year":"2012","journal-title":"Bioinformatics"},{"key":"pntd.0009991.ref155","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modelling by satisfaction of spatial restraints","volume":"234","author":"A Sali","year":"1993","journal-title":"J Mol Biol"},{"key":"pntd.0009991.ref156","doi-asserted-by":"crossref","first-page":"5.6.1","DOI":"10.1002\/cpbi.3","article-title":"Comparative Protein Structure Modeling Using MODELLER","volume":"54","author":"B Webb","year":"2016","journal-title":"Curr Protoc Bioinforma"},{"key":"pntd.0009991.ref157","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.chembiol.2018.01.008","article-title":"Structural Basis for Inhibitor-Induced Hydrogen Peroxide Production by Kynurenine 3-Monooxygenase","volume":"25","author":"HT Kim","year":"2018","journal-title":"Cell Chem Biol"},{"key":"pntd.0009991.ref158","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1021\/jm8010806","article-title":"Crystal Structure of the Homo sapiens Kynureninase-3-Hydroxyhippuric Acid Inhibitor Complex: Insights into the Molecular Basis Of Kynureninase Substrate Specificity","volume":"52","author":"S Lima","year":"2009","journal-title":"J Med Chem"},{"key":"pntd.0009991.ref159","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1042\/BJ20150329","article-title":"Structural and biochemical studies reveal UbiG\/Coq3 as a class of novel membrane-binding proteins","volume":"470","author":"Y Zhu","year":"2015","journal-title":"Biochem J"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0009991","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0009991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T09:34:55Z","timestamp":1699868095000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0009991"}},"subtitle":[],"editor":[{"given":"Aaron R.","family":"Jex","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,11,29]]},"references-count":159,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0009991","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0009991","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,29]]}}}