{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:28:51Z","timestamp":1780471731324,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1008909","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000}}],"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein and is essential in all eukaryotes. However, the specific roles of eIF5A in translation and in other biological processes remain elusive. In the present study, we described the role of eIF5A, its posttranslational modifications (PTM), and the biosynthetic pathway needed for the PTM in\n                    <jats:italic>Entamoeba histolytica<\/jats:italic>\n                    , the protozoan parasite responsible for amoebic dysentery and liver abscess in humans.\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>histolytica<\/jats:italic>\n                    encodes two isotypes of eIF5A and two isotypes of enzymes, deoxyhypusine synthase (DHS), responsible for their PTM. Both of the two eIF5A isotypes are functional, whereas only one DHS (EhDHS1, but not EhDHS2), is catalytically active. The DHS activity increased ~2000-fold when EhDHS1 was co-expressed with EhDHS2 in\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , suggesting that the formation of a heteromeric complex is needed for full enzymatic activity. Both\n                    <jats:italic>EhDHS1<\/jats:italic>\n                    and\n                    <jats:italic>2<\/jats:italic>\n                    genes were required for\n                    <jats:italic>in vitro<\/jats:italic>\n                    growth of\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>histolytica<\/jats:italic>\n                    trophozoites, indicated by small antisense RNA-mediated gene silencing. In trophozoites, only\n                    <jats:italic>eIF5A2<\/jats:italic>\n                    , but not\n                    <jats:italic>eIF5A1<\/jats:italic>\n                    , gene was actively transcribed. Gene silencing of\n                    <jats:italic>eIF5A2<\/jats:italic>\n                    caused compensatory induction of expression of\n                    <jats:italic>eIF5A1<\/jats:italic>\n                    gene, suggesting interchangeable role of the two eIF5A isotypes and also reinforcing the importance of eIF5As for parasite proliferation and survival. Furthermore, using a sibling species,\n                    <jats:italic>Entamoeba invadens<\/jats:italic>\n                    , we found that\n                    <jats:italic>eIF5A1<\/jats:italic>\n                    gene was upregulated during excystation, while\n                    <jats:italic>eIF5A2<\/jats:italic>\n                    was downregulated, suggesting that\n                    <jats:italic>eIF5A1<\/jats:italic>\n                    gene plays an important role during differentiation. Taken together, these results have underscored the essentiality of eIF5A and DHS, for proliferation and potentially in the differentiation of this parasite, and suggest that the hypusination associated pathway represents a novel rational target for drug development against amebiasis.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1008909","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T17:33:52Z","timestamp":1613496832000},"page":"e1008909","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Eukaryotic translation initiation factor 5A and its posttranslational modifications play an important role in proliferation and potentially in differentiation of the human enteric protozoan parasite Entamoeba histolytica"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0816-9831","authenticated-orcid":true,"given":"Ghulam","family":"Jeelani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1354-5133","authenticated-orcid":true,"given":"Tomoyoshi","family":"Nozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"ppat.1008909.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1432-0436.1981.tb01123.x","article-title":"Role of polyamines in the control of cell proliferation and differentiation","volume":"19","author":"O. Heby","year":"1981","journal-title":"Differentiation"},{"key":"ppat.1008909.ref002","doi-asserted-by":"crossref","first-page":"14904","DOI":"10.1074\/jbc.R116.731661","article-title":"Functions of polyamines in mammals","volume":"291","author":"AE Pegg","year":"2016","journal-title":"J. Biol. Chem"},{"key":"ppat.1008909.ref003","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1242\/bio.016352","article-title":"Plasmodium AdoMetDC\/ODC bifunctional enzyme is essential for male sexual stage development and mosquito transmission","volume":"5","author":"RJ Hart","year":"2016","journal-title":"Biol Open"},{"key":"ppat.1008909.ref004","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/jb\/mvj034","article-title":"The post-translational synthesis of a polyamine-derived amino acid, hypusine, in the eukaryotic translation initiation factor 5A (eIF5A)","volume":"139","author":"MH Park","year":"2006","journal-title":"J. Biochem. (Tokyo)"},{"key":"ppat.1008909.ref005","first-page":"233","article-title":"Posttranslational synthesis of hypusine: Evolutionary progression and specificity of the hypusine modification","volume":"71","author":"EC Wolff","year":"2007","journal-title":"Amino Acids"},{"key":"ppat.1008909.ref006","doi-asserted-by":"crossref","first-page":"18710","DOI":"10.1074\/jbc.TM118.003341","article-title":"Hypusine, a polyamine-derived amino acid critical for eukaryotic translation","volume":"293","author":"MH Park","year":"2018","journal-title":"J. Biol.Chem"},{"key":"ppat.1008909.ref007","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nature08034","article-title":"Hypusine-containing Protein eIF5A Promotes Translation Elongation","volume":"459","author":"P Saini","year":"2011","journal-title":"Nature"},{"key":"ppat.1008909.ref008","doi-asserted-by":"crossref","first-page":"7326","DOI":"10.1093\/nar\/gkx479","article-title":"EIF5A facilitates translation termination globally and promotes the elongation of many non polyproline-specific tripeptide sequences","volume":"45","author":"V Pelechano","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"ppat.1008909.ref009","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/mmi.13233","article-title":"Stall no more at polyproline stretches with the translation elongation factors EF-P and IF-5A","volume":"99","author":"J Lassak","year":"2016","journal-title":"Mol. Microbiol"},{"key":"ppat.1008909.ref010","doi-asserted-by":"crossref","first-page":"e111800","DOI":"10.1371\/journal.pone.0111800","article-title":"Genome-wide analyses and functional classification of proline repeat-rich proteins: Potential role of eIF5A in eukaryotic evolution","volume":"9","author":"A Mandal","year":"2014","journal-title":"PLoS ONE"},{"key":"ppat.1008909.ref011","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.meegid.2009.06.008","article-title":"Reassessment of the epidemiology of amebiasis: state of the art","volume":"9","author":"C Ximenez","year":"2009","journal-title":"Infect Genet Evol"},{"key":"ppat.1008909.ref012","doi-asserted-by":"crossref","first-page":"e1247","DOI":"10.1371\/journal.pntd.0001247","article-title":"Glucose starvation boosts Entamoeba histolytica virulence","volume":"5","author":"A Tovy","year":"2011","journal-title":"PLoS Negl. Trop. 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Sci"},{"key":"ppat.1008909.ref016","doi-asserted-by":"crossref","first-page":"15256","DOI":"10.1074\/jbc.M113.461137","article-title":"Allosteric activation of trypanosomatid deoxyhypusine synthase by a catalytically dead paralog","volume":"288","author":"S Nguyen","year":"2013","journal-title":"J. Biol. Chem"},{"key":"ppat.1008909.ref017","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1074\/jbc.M109.048850","article-title":"Identification and characterization of a novel deoxyhypusine synthase in Leishmania donovani","volume":"285","author":"B Chawla","year":"2010","journal-title":"J. Biol. Chem"},{"key":"ppat.1008909.ref018","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1016\/j.str.2018.07.012","article-title":"Trypanosomatid Deoxyhypusine Synthase Activity Is Dependent on Shared Active-Site Complementation between Pseudoenzyme Paralogs","volume":"26","author":"GA Afanador","year":"2018","journal-title":"Structure"},{"key":"ppat.1008909.ref019","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0969-2126(98)00004-5","article-title":"Crystal structure of the NAD complex of human deoxyhypusine synthase: an enzyme with a ball-and-chain mechanism for blocking the active site","volume":"6","author":"DI Liao","year":"1998","journal-title":"Structure"},{"key":"ppat.1008909.ref020","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/j.1742-4658.2007.06172.x","article-title":"Mutational analyses of human eIF5A-1\u2014identification of amino acid residues critical for eIF5A activity and hypusine modification","volume":"275","author":"VS Cano","year":"2008","journal-title":"FEBS J"},{"key":"ppat.1008909.ref021","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1271\/bbb.120620","article-title":"The role of acetylation in the subcellular localization of an oncogenic isoform of translation factor eIF5A","volume":"76","author":"M Ishfaq","year":"2012","journal-title":"Biosci Biotechnol Biochem"},{"key":"ppat.1008909.ref022","doi-asserted-by":"crossref","first-page":"13737","DOI":"10.1038\/srep13737","article-title":"Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis","volume":"5","author":"Y Seko","year":"2015","journal-title":"Sci Rep"},{"key":"ppat.1008909.ref023","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-1-61779-034-8_12","article-title":"Assay of deoxyhypusine synthase activity","volume":"720","author":"EC Wolff","year":"2011","journal-title":"Methods Mol Biol"},{"key":"ppat.1008909.ref024","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1042\/BJ20040958","article-title":"Efficient co-expression of a recombinant staphopain A and its inhibitor staphostatin A in Escherichia coli","volume":"385","author":"B Wladyka","year":"2005","journal-title":"Biochem J"},{"issue":"2","key":"ppat.1008909.ref025","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.pep.2010.06.018","article-title":"Over-expression and purification strategies for recombinant multi-protein oligomers: a case study of Mycobacterium tuberculosis \u03c3\/anti-\u03c3 factor protein complexes","volume":"74","author":"KG Thakur","year":"2010","journal-title":"Protein Expr Purif"},{"key":"ppat.1008909.ref026","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1128\/EC.2.2.295-305.2003","article-title":"Transcriptional silencing of an amoebapore gene in Entamoeba histolytica: molecular analysis and effect on pathogenicity","volume":"2","author":"R Bracha","year":"2003","journal-title":"Eukaryot Cell"},{"key":"ppat.1008909.ref027","doi-asserted-by":"crossref","first-page":"e48","DOI":"10.1371\/journal.ppat.0020048","article-title":"Transcriptional silencing of multiple genes in trophozoites of Entamoeba histolytica","volume":"2","author":"R Bracha","year":"2006","journal-title":"PLoS Pathog"},{"key":"ppat.1008909.ref028","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1186\/2193-1801-2-421","article-title":"Characterization of a novel polyclonal anti-hypusine antibody","volume":"2","author":"Y Nishiki","year":"2013","journal-title":"Springerplus."},{"key":"ppat.1008909.ref029","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0166-6851(98)00129-7","article-title":"Molecular cloning and characterization of the genes encoding two isoforms of cysteine synthase in the enteric protozoan parasite Entamoeba histolytica","volume":"97","author":"T Nozaki","year":"1998","journal-title":"Mol Biochem Parasitol"},{"key":"ppat.1008909.ref030","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1111\/j.1462-5822.2012.01800.x","article-title":"A novel class of cysteine protease receptors that mediate lysosomal transport","volume":"14","author":"K Nakada-Tsukui","year":"2012","journal-title":"Cell Microbiol"},{"key":"ppat.1008909.ref031","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s11010-011-0952-9","article-title":"Phosphorylation of maize eukaryotic translation initiation factor on Ser2 by catalytic subunit CK2","volume":"356","author":"E Lewandowska-Gnatowska","year":"2011","journal-title":"Mol Cell Biochem"},{"key":"ppat.1008909.ref032","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.micpath.2011.12.004","article-title":"Translation initiation factor eIF-5A, the hypusine-containing protein, is phosphorylated on serine and tyrosine and O-glycosylated in Trichomonas vaginalis","volume":"52","author":"BI Carvajal-Gamez","year":"2012","journal-title":"Microb Pathog"},{"issue":"1","key":"ppat.1008909.ref033","doi-asserted-by":"crossref","first-page":"15649","DOI":"10.1038\/s41598-017-15923-3","article-title":"Genetic, metabolomic and transcriptomic analyses of the de novo L-cysteine biosynthetic pathway in the enteric protozoan parasite Entamoeba histolytica","volume":"7","author":"G Jeelani","year":"2017","journal-title":"Sci Rep"},{"key":"ppat.1008909.ref034","doi-asserted-by":"crossref","first-page":"e1006085","DOI":"10.1371\/journal.ppat.1006085","article-title":"Phosphorylation of Eukaryotic Initiation Factor-2\u03b1 during Stress and Encystation in Entamoeba Species","volume":"12","author":"HM Hendrick","year":"2016","journal-title":"PLoS Pathog"},{"key":"ppat.1008909.ref035","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/jcp.22229","article-title":"Evidences of a role for eukaryotic translation initiation factor 5A (eIF5A) in mouse embryogenesis and cell differentiation","volume":"225","author":"LT Parreiras-e-Silva","year":"2010","journal-title":"J Cell Physiol"},{"key":"ppat.1008909.ref036","doi-asserted-by":"crossref","first-page":"R77","DOI":"10.1186\/gb-2013-14-7-r77","article-title":"The genome and transcriptome of the enteric parasite Entamoeba invadens, a model for encystation","volume":"14","author":"GM Ehrenkaufer","year":"2013","journal-title":"Genome Biol"},{"issue":"9","key":"ppat.1008909.ref037","doi-asserted-by":"crossref","first-page":"e74840","DOI":"10.1371\/journal.pone.0074840","article-title":"Transcriptome analysis of encystation in Entamoeba invadens","volume":"8","author":"AE De C\u00e1diz","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"ppat.1008909.ref038","first-page":"3","article-title":"Giardia lamblia\u2014a model organism for eukaryotic cell differentiation","volume":"218","author":"SG Sv\u00e4rd","year":"2003","journal-title":"FEMS Microbiol Lett"},{"key":"ppat.1008909.ref039","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1111\/j.1742-4658.2006.05135.x","article-title":"Differential expression of eIF5A-1 and eIF5A-2 in human cancer cells","volume":"273","author":"PM Clement","year":"2006","journal-title":"FEBS J"},{"key":"ppat.1008909.ref040","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1042\/bj3400273","article-title":"Complex formation between deoxyhypusine synthase and its protein substrate, the eukaryotic translation initiation factor 5A (eIF5A) precursor","volume":"340","author":"YB Lee","year":"1999","journal-title":"Biochem J"},{"key":"ppat.1008909.ref041","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/jb\/mvg011","article-title":"Crystal structure of hyperthermophilic archaeal initiation factor 5A: a homologue of eukaryotic initiation factor 5A (eIF-5A)","volume":"133","author":"M Yao","year":"2003","journal-title":"J Biochem"},{"key":"ppat.1008909.ref042","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1271\/bbb.120620","article-title":"The role of acetylation in the subcellular localization of an oncogenic isoform of translation factor eIF5A","volume":"76","author":"M Ishfaq","year":"2012","journal-title":"Bioscience, biotechnology, and biochemistry"},{"key":"ppat.1008909.ref043","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1042\/bj3050725","article-title":"Identification of a substrate site for transglutaminases on the human protein synthesis initiation factor 5A","volume":"305","author":"S Beninati","year":"1995","journal-title":"Biochem J"},{"issue":"6","key":"ppat.1008909.ref044","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.gpb.2013.07.004","article-title":"Identification of the phosphorylated residues in TveIF5A by mass spectrometry","volume":"11","author":"LI Quintas-Granados","year":"2013","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"ppat.1008909.ref045","doi-asserted-by":"crossref","first-page":"6217","DOI":"10.1074\/jbc.M109.018770","article-title":"Phosphorylation of maize eukaryotic translation initiation factor 5A (eIF5A) by casein kinase 2: identification of phosphorylated residue and influence on intracellular localization of eIF5A","volume":"285","author":"M \u0141ebska","year":"2010","journal-title":"J Biol Chem"},{"key":"ppat.1008909.ref046","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1074\/mcp.M112.019059","article-title":"Protein-protein-interaction network organization of the hypusine modification system","volume":"11","author":"H Sievert","year":"2012","journal-title":"Mol Cell Proteomics"},{"key":"ppat.1008909.ref047","doi-asserted-by":"crossref","first-page":"3236","DOI":"10.1016\/j.febslet.2012.06.042","article-title":"Acetylation regulates subcellular localization of eukaryotic translation initiation factor 5A (eIF5A)","volume":"586","author":"M Ishfaq","year":"2012","journal-title":"FEBS Lett"},{"key":"ppat.1008909.ref048","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1006\/excr.1996.0185","article-title":"The subcellular distribution of eukaryotic translation initiation factor, eIF-5A, in cultured cells","volume":"225","author":"XP Shi","year":"1996","journal-title":"Exp. Cell Res"},{"key":"ppat.1008909.ref049","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1242\/jcs.112.14.2369","article-title":"Nuclear pore localization and nucleocytoplasmic transport of eIF-5A: evidence for direct interaction with the export receptor CRM1","volume":"112","author":"O Rosorius","year":"1999","journal-title":"J. Cell Sci"},{"issue":"3","key":"ppat.1008909.ref050","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/jcb.10235","article-title":"Subcellular localization of the hypusine-containing eukaryotic initiation factor 5A by immunofluorescent staining and green fluorescent protein tagging","volume":"86","author":"DL Jao","year":"2002","journal-title":"J Cell Biochem"},{"key":"ppat.1008909.ref051","doi-asserted-by":"crossref","first-page":"4362","DOI":"10.1093\/emboj\/19.16.4362","article-title":"Exportin 4: a mediator of a novel nuclear export pathway in higher eukaryotes","volume":"19","author":"G Lipowsky","year":"2000","journal-title":"EMBO J"},{"key":"ppat.1008909.ref052","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.cell.2008.09.061","article-title":"An oncogenomics-based in vivo RNAi screen identifies tumor suppressors in liver cancer","volume":"135","author":"L Zender","year":"2008","journal-title":"Cell"},{"key":"ppat.1008909.ref053","doi-asserted-by":"crossref","first-page":"11952","DOI":"10.1038\/ncomms11952","article-title":"Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A","volume":"7","author":"M Aksu","year":"2016","journal-title":"Nat Commun"},{"key":"ppat.1008909.ref054","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1159\/000109115","article-title":"Biochemistry and function of hypusine formation on eukaryotic initiation factor 5A","volume":"6","author":"KY Chen","year":"1997","journal-title":"Biol. Signals"},{"key":"ppat.1008909.ref055","doi-asserted-by":"crossref","first-page":"4254","DOI":"10.1046\/j.1432-1033.2003.03806.x","article-title":"Identification and characterization of eukaryotic initiation factor 5A-2","volume":"147","author":"PC Clement","year":"2003","journal-title":"Eur. J. Biochem"},{"key":"ppat.1008909.ref056","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1006\/geno.2000.6418","article-title":"Human EIF5A2 on chromosome 3q25\u2013q27 is a phylogenetically conserved vertebrate variant of eukaryotic translation initiation factor 5A with tissue-specific expression","volume":"71","author":"ZA Jenkins","year":"2001","journal-title":"Genomics"},{"key":"ppat.1008909.ref057","doi-asserted-by":"crossref","first-page":"4254","DOI":"10.1046\/j.1432-1033.2003.03806.x","article-title":"Identification and characterization of eukaryotic initiation factor 5A-2","volume":"270","author":"PM Clement","year":"2003","journal-title":"Eur J Biochem"},{"key":"ppat.1008909.ref058","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.bbagrm.2015.05.002","article-title":"The translation factor eIF5A and human cancer","volume":"1849","author":"MB Mathews","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"ppat.1008909.ref059","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s00726-009-0408-7","article-title":"Functional significance of eIF5A and its hypusine modification in eukaryotes","volume":"38","author":"MH Park","year":"2010","journal-title":"Amino Acids"},{"key":"ppat.1008909.ref060","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0014-5793(96)00310-9","article-title":"Deoxyhypusine synthase gene is essential for cell viability in the yeast Saccharomyces cerevisiae","volume":"384","author":"K Sasaki","year":"1996","journal-title":"FEBS Lett"},{"key":"ppat.1008909.ref061","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1074\/jbc.273.3.1677","article-title":"Deoxyhypusine synthase activity is essential for cell viability in the yeast Saccharomyces cerevisiae","volume":"273","author":"MH Park","year":"1998","journal-title":"J Biol Chem"},{"key":"ppat.1008909.ref062","doi-asserted-by":"crossref","first-page":"e1006780","DOI":"10.1371\/journal.pgen.1006780","article-title":"Genetic compensation: A phenomenon in search of mechanisms","volume":"13","author":"MA El-Brolosy","year":"2017","journal-title":"PLoS Genet"},{"key":"ppat.1008909.ref063","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0035-9203(78)90144-X","article-title":"A new medium for the axenic cultivation of Entamoeba histolytica and other Entamoeba","volume":"72","author":"LS Diamond","year":"1978","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ppat.1008909.ref064","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","article-title":"CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice","volume":"22","author":"JD Thompson","year":"1999","journal-title":"Nucleic Acids Res"},{"key":"ppat.1008909.ref065","author":"J Sambrook","year":"2001","edition":"3"},{"key":"ppat.1008909.ref066","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein\u2013dye binding","volume":"72","author":"MM Bradford","year":"1976","journal-title":"Anal. 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Microbiol"},{"key":"ppat.1008909.ref069","doi-asserted-by":"crossref","first-page":"32445","DOI":"10.1074\/jbc.274.45.32445","article-title":"Characterization of the gene encoding serine acetyltransferase, a regulated enzyme of cysteine biosynthesis from the protist parasites Entamoeba histolytica and Entamoeba dispar. Regulation and possible function of the cysteine biosynthetic pathway in Entamoeba","volume":"274","author":"T Nozaki","year":"1999","journal-title":"J. Biol. 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