{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:04:27Z","timestamp":1790708667356,"version":"4.1.0"},"reference-count":126,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"publisher","award":["FDN 143277"],"award-info":[{"award-number":["FDN 143277"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>KEOPS (Kinase, Endopeptidase and Other Proteins of Small size) is a five-subunit protein complex that is highly conserved in eukaryotes and archaea and is essential for the fitness of cells and for\u00a0animal development. In humans, mutations in KEOPS genes underlie Galloway\u2013Mowat syndrome, which manifests in severe microcephaly and renal dysfunction that lead to childhood death. The Kae1 subunit of KEOPS catalyzes the universal and essential tRNA modification N6-threonylcarbamoyl adenosine (t6A), while the auxiliary subunits Cgi121, the kinase\/ATPase Bud32, Pcc1 and Gon7 play a supporting role. Kae1 orthologs are also present in bacteria and mitochondria but function in distinct complexes with proteins that are not related in structure or function to the auxiliary subunits of KEOPS. Over the past 15 years since its discovery, extensive study in the KEOPS field has provided many answers towards understanding the roles that KEOPS plays in cells and in human disease and how KEOPS carries out these functions. In this review, we provide an overview into recent advances in the study of KEOPS and illuminate exciting future directions.<\/jats:p>","DOI":"10.1093\/nar\/gkab865","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:58:38Z","timestamp":1633481918000},"page":"10818-10834","source":"Crossref","is-referenced-by-count":44,"title":["The structural and functional workings of KEOPS"],"prefix":"10.1093","volume":"49","author":[{"given":"Jonah","family":"Beenstock","sequence":"first","affiliation":[{"name":"The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario,\u00a0M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9824-2117","authenticated-orcid":false,"given":"Frank","family":"Sicheri","sequence":"additional","affiliation":[{"name":"The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario,\u00a0M5G 1X5, Canada"},{"name":"Department of Molecular Genetics, University of Toronto, Ontario, M5S 1A8, Canada"},{"name":"Department of Biochemistry, University of Toronto, Ontario, M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"2021110312483238100_B1","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.cell.2005.12.044","article-title":"A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator","volume":"124","author":"Downey","year":"2006","journal-title":"Cell"},{"key":"2021110312483238100_B2","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1038\/sj.emboj.7601235","article-title":"Yeast homolog of a cancer-testis antigen defines a new transcription complex","volume":"25","author":"Kisseleva-Romanova","year":"2006","journal-title":"EMBO J."},{"key":"2021110312483238100_B3","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nrmicro751","article-title":"Comparative genomics, minimal gene-sets and the last universal common ancestor","volume":"1","author":"Koonin","year":"2003","journal-title":"Nat. Rev. Microbiol."},{"key":"2021110312483238100_B4","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1091\/mbc.12.7.2147","article-title":"A genomic study of the bipolar bud site selection pattern in Saccharomyces cerevisiae","volume":"12","author":"Ni","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"2021110312483238100_B5","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0014-5793(97)00980-0","article-title":"Biochemical evidence that Saccharomyces cerevisiae YGR262c gene, required for normal growth, encodes a novel Ser\/Thr-specific protein kinase","volume":"414","author":"Stocchetto","year":"1997","journal-title":"FEBS Lett."},{"key":"2021110312483238100_B6","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.tibs.2015.09.002","article-title":"Dynamics-driven allostery in protein kinases","volume":"40","author":"Kornev","year":"2015","journal-title":"Trends Biochem. 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J."},{"key":"2021110312483238100_B12","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1371\/journal.pbio.0050017","article-title":"Structural and functional diversity of the microbial kinome","volume":"5","author":"Kannan","year":"2007","journal-title":"PLoS Biol."},{"key":"2021110312483238100_B13","doi-asserted-by":"crossref","first-page":"9480","DOI":"10.1074\/jbc.R113.529412","article-title":"Protein Ser\/Thr\/Tyr phosphorylation in the Archaea","volume":"289","author":"Kennelly","year":"2014","journal-title":"J. Biol. Chem."},{"key":"2021110312483238100_B14","doi-asserted-by":"crossref","first-page":"44003","DOI":"10.1074\/jbc.M105669200","article-title":"Cloning and characterization of a p53-related protein kinase expressed in interleukin-2-activated cytotoxic T-cells, epithelial tumor cell lines, and the testes","volume":"276","author":"Abe","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021110312483238100_B15","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0006-291X(03)00333-4","article-title":"Identification of CGI-121, a novel PRPK (p53-related protein kinase)-binding protein","volume":"303","author":"Miyoshi","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021110312483238100_B16","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1101\/gr.10.5.703","article-title":"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics","volume":"10","author":"Lai","year":"2000","journal-title":"Genome Res."},{"key":"2021110312483238100_B17","doi-asserted-by":"crossref","first-page":"5597","DOI":"10.1128\/jb.173.18.5597-5603.1991","article-title":"Cloning, nucleotide sequence, and expression of the Pasteurella haemolytica A1 glycoprotease gene","volume":"173","author":"Abdullah","year":"1991","journal-title":"J. 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VII. N-(Purin-6-ylcarbamoyl)threonine. A new component of transfer ribonucleic acid","volume":"8","author":"Schweizer","year":"1969","journal-title":"Biochemistry"},{"key":"2021110312483238100_B36","doi-asserted-by":"crossref","first-page":"8078","DOI":"10.1021\/bi050343f","article-title":"Structural effects of hypermodified nucleosides in the Escherichia coli and human tRNALys anticodon loop: the effect of nucleosides s2U, mcm5U, mcm5s2U, mnm5s2U, t6A, and ms2t6A","volume":"44","author":"Durant","year":"2005","journal-title":"Biochemistry"},{"key":"2021110312483238100_B37","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1093\/nar\/gkl081","article-title":"The naturally occurring N6-threonyl adenine in anticodon loop of Schizosaccharomyces pombe tRNAi causes formation of a unique U-turn motif","volume":"34","author":"Lescrinier","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B38","doi-asserted-by":"crossref","first-page":"13396","DOI":"10.1021\/bi0013039","article-title":"Functional anticodon architecture of human tRNALys3 includes disruption of intraloop hydrogen bonding by the naturally occurring amino acid modification, t6A","volume":"39","author":"Stuart","year":"2000","journal-title":"Biochemistry"},{"key":"2021110312483238100_B39","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1261\/rna.078097.120","article-title":"Posttranscriptional modifications at the 37th position in the anticodon stem-loop of tRNA: structural insights from MD simulations","volume":"27","author":"Seelam\u00a0Prabhakar","year":"2021","journal-title":"RNA"},{"key":"2021110312483238100_B40","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1038\/nsmb861","article-title":"The role of modifications in codon discrimination by tRNA(Lys)UUU","volume":"11","author":"Murphy","year":"2004","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2021110312483238100_B41","doi-asserted-by":"crossref","first-page":"13390","DOI":"10.1021\/bi001302g","article-title":"Modified nucleoside dependent Watson-Crick and wobble codon binding by tRNALysUUU species","volume":"39","author":"Yarian","year":"2000","journal-title":"Biochemistry"},{"key":"2021110312483238100_B42","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1432-1033.1981.tb05320.x","article-title":"Effect of threonylcarbamoyl modification (t6A) in yeast tRNA Arg III on codon-anticodon and anticodon-anticodon interactions. A thermodynamic and kinetic evaluation","volume":"116","author":"Weissenbach","year":"1981","journal-title":"Eur. J. Biochem."},{"key":"2021110312483238100_B43","doi-asserted-by":"crossref","first-page":"8020","DOI":"10.1093\/nar\/gkw608","article-title":"An integrated, structure- and energy-based view of the genetic code","volume":"44","author":"Grosjean","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B44","doi-asserted-by":"crossref","first-page":"29","DOI":"10.15698\/mic2016.01.473","article-title":"Global translational impacts of the loss of the tRNA modification t(6)A in yeast","volume":"3","author":"Thiaville","year":"2016","journal-title":"Microb Cell"},{"key":"2021110312483238100_B45","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1128\/MCB.00754-09","article-title":"The Sua5 protein is essential for normal translational regulation in yeast","volume":"30","author":"Lin","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"2021110312483238100_B46","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/emboj.2010.363","article-title":"A role for the universal Kae1\/Qri7\/YgjD (COG0533) family in tRNA modification","volume":"30","author":"El\u00a0Yacoubi","year":"2011","journal-title":"EMBO J."},{"key":"2021110312483238100_B47","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1093\/nar\/gkp152","article-title":"The universal YrdC\/Sua5 family is required for the formation of threonylcarbamoyladenosine in tRNA","volume":"37","author":"El\u00a0Yacoubi","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B48","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nchembio.1137","article-title":"A cyclic form of N6-threonylcarbamoyladenosine as a widely distributed tRNA hypermodification","volume":"9","author":"Miyauchi","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"2021110312483238100_B49","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1093\/nar\/gkw1189","article-title":"A hydantoin isoform of cyclic N6-threonylcarbamoyladenosine (ct6A) is present in tRNAs","volume":"45","author":"Matuszewski","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B50","doi-asserted-by":"crossref","first-page":"9350","DOI":"10.1093\/nar\/gku618","article-title":"Discovery of the beta-barrel-type RNA methyltransferase responsible for N6-methylation of N6-threonylcarbamoyladenosine in tRNAs","volume":"42","author":"Kimura","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B51","doi-asserted-by":"crossref","first-page":"3598","DOI":"10.1172\/JCI58056","article-title":"Deficit of tRNA(Lys) modification by Cdkal1 causes the development of type 2 diabetes in mice","volume":"121","author":"Wei","year":"2011","journal-title":"J. Clin. Invest."},{"key":"2021110312483238100_B52","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1093\/genetics\/131.4.791","article-title":"Isolation and characterization of SUA5, a novel gene required for normal growth in Saccharomyces cerevisiae","volume":"131","author":"Na","year":"1992","journal-title":"Genetics"},{"key":"2021110312483238100_B53","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1006\/jmbi.1999.2653","article-title":"Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches","volume":"287","author":"Aravind","year":"1999","journal-title":"J. Mol. Biol."},{"key":"2021110312483238100_B54","doi-asserted-by":"crossref","first-page":"12047","DOI":"10.1074\/jbc.273.20.12047","article-title":"nolO and noeI (HsnIII) of Rhizobium sp. NGR234 are involved in 3-O-carbamoylation and 2-O-methylation of Nod factors","volume":"273","author":"Jabbouri","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2021110312483238100_B55","doi-asserted-by":"crossref","first-page":"6148","DOI":"10.1093\/nar\/gkr178","article-title":"Gcn4 misregulation reveals a direct role for the evolutionary conserved EKC\/KEOPS in the t6A modification of tRNAs","volume":"39","author":"Daugeron","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B56","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/emboj.2010.343","article-title":"The highly conserved KEOPS\/EKC complex is essential for a universal tRNA modification, t6A","volume":"30","author":"Srinivasan","year":"2011","journal-title":"EMBO J."},{"key":"2021110312483238100_B57","doi-asserted-by":"crossref","first-page":"5452","DOI":"10.1093\/nar\/gkh885","article-title":"Conserved hypothetical\u2019 proteins: prioritization of targets for experimental study","volume":"32","author":"Galperin","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B58","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev.micro.59.031805.133833","article-title":"Translational regulation of GCN4 and the general amino acid control of yeast","volume":"59","author":"Hinnebusch","year":"2005","journal-title":"Annu. Rev. Microbiol."},{"key":"2021110312483238100_B59","doi-asserted-by":"crossref","first-page":"13666","DOI":"10.1074\/jbc.M112.344028","article-title":"Biosynthesis of threonylcarbamoyl adenosine (t6A), a universal tRNA nucleoside","volume":"287","author":"Deutsch","year":"2012","journal-title":"J. Biol. Chem."},{"key":"2021110312483238100_B60","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1093\/nar\/gks1287","article-title":"In vitro biosynthesis of a universal t6A tRNA modification in Archaea and Eukarya","volume":"41","author":"Perrochia","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B61","doi-asserted-by":"crossref","first-page":"6332","DOI":"10.1093\/nar\/gkt322","article-title":"Reconstitution and characterization of eukaryotic N6-threonylcarbamoylation of tRNA using a minimal enzyme system","volume":"41","author":"Wan","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B62","doi-asserted-by":"crossref","first-page":"322","DOI":"10.3390\/biom10020322","article-title":"Loss of Elongator- and KEOPS-Dependent tRNA Modifications Leads to Severe Growth Phenotypes and Protein Aggregation in Yeast","volume":"10","author":"Pollo-Oliveira","year":"2020","journal-title":"Biomolecules"},{"key":"2021110312483238100_B63","doi-asserted-by":"crossref","first-page":"e1005071","DOI":"10.1371\/journal.pgen.1005071","article-title":"Inhibition of telomere recombination by inactivation of KEOPS subunit Cgi121 promotes cell longevity","volume":"11","author":"Peng","year":"2015","journal-title":"PLos Genet."},{"key":"2021110312483238100_B64","doi-asserted-by":"crossref","first-page":"10331","DOI":"10.1093\/nar\/gky664","article-title":"Codon-specific effects of tRNA anticodon loop modifications on translational misreading errors in the yeast Saccharomyces cerevisiae","volume":"46","author":"Joshi","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B65","doi-asserted-by":"crossref","first-page":"e43013","DOI":"10.1371\/journal.pone.0043013","article-title":"A genetic investigation of the KEOPS complex in halophilic Archaea","volume":"7","author":"Naor","year":"2012","journal-title":"PLoS One"},{"key":"2021110312483238100_B66","first-page":"25","article-title":"Modulation of the proteostasis machinery to overcome stress caused by diminished levels of t6A-modified tRNAs in Drosophila","volume":"7","author":"Rojas-Benitez","year":"2017","journal-title":"Biomolecules"},{"key":"2021110312483238100_B67","doi-asserted-by":"crossref","first-page":"168","DOI":"10.4161\/fly.25227","article-title":"The Drosophila EKC\/KEOPS complex: roles in protein synthesis homeostasis and animal growth","volume":"7","author":"Rojas-Benitez","year":"2013","journal-title":"Fly (Austin)"},{"key":"2021110312483238100_B68","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1261\/rna.053934.115","article-title":"An extensive allelic series of Drosophila kae1 mutants reveals diverse and tissue-specific requirements for t6A biogenesis","volume":"21","author":"Lin","year":"2015","journal-title":"RNA"},{"key":"2021110312483238100_B69","doi-asserted-by":"crossref","first-page":"18699","DOI":"10.1074\/jbc.M115.665406","article-title":"The Levels of a Universally Conserved tRNA Modification Regulate Cell Growth","volume":"290","author":"Rojas-Benitez","year":"2015","journal-title":"J. Biol. Chem."},{"key":"2021110312483238100_B70","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1242\/dev.086918","article-title":"Drosophila p53-related protein kinase is required for PI3K\/TOR pathway-dependent growth","volume":"140","author":"Ibar","year":"2013","journal-title":"Development"},{"key":"2021110312483238100_B71","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1101\/gad.835000","article-title":"Regulation of cellular growth by the Drosophila target of rapamycin dTOR","volume":"14","author":"Zhang","year":"2000","journal-title":"Genes Dev."},{"key":"2021110312483238100_B72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15698\/mic2015.01.185","article-title":"The emerging role of complex modifications of tRNA(Lys)UUU in signaling pathways","volume":"2","author":"Thiaville","year":"2015","journal-title":"Microb Cell"},{"key":"2021110312483238100_B73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20110892","article-title":"Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks","volume":"441","author":"Magnuson","year":"2012","journal-title":"Biochem. J."},{"key":"2021110312483238100_B74","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1038\/ng.3933","article-title":"Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly","volume":"49","author":"Braun","year":"2017","journal-title":"Nat. Genet."},{"key":"2021110312483238100_B75","doi-asserted-by":"crossref","first-page":"e0191503","DOI":"10.1371\/journal.pone.0191503","article-title":"Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly phenotype of the stable knockout zebrafish model","volume":"13","author":"Jobst-Schwan","year":"2018","journal-title":"PLoS One"},{"key":"2021110312483238100_B76","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/ejhg.2017.30","article-title":"tRNA N6-adenosine threonylcarbamoyltransferase defect due to KAE1\/TCS3 (OSGEP) mutation manifest by neurodegeneration and renal tubulopathy","volume":"25","author":"Edvardson","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"2021110312483238100_B77","doi-asserted-by":"crossref","first-page":"3967","DOI":"10.1038\/s41467-019-11951-x","article-title":"Defects in t(6)A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome","volume":"10","author":"Arrondel","year":"2019","journal-title":"Nat. Commun."},{"key":"2021110312483238100_B78","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1136\/jmg.5.4.319","article-title":"Congenital microcephaly with hiatus hernia and nephrotic syndrome in two sibs","volume":"5","author":"Galloway","year":"1968","journal-title":"J. Med. Genet."},{"key":"2021110312483238100_B79","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/s41467-019-14004-5","article-title":"Irp2 regulates insulin production through iron-mediated Cdkal1-catalyzed tRNA modification","volume":"11","author":"Santos","year":"2020","journal-title":"Nat. Commun."},{"key":"2021110312483238100_B80","doi-asserted-by":"crossref","first-page":"4622","DOI":"10.1021\/bi00719a024","article-title":"The enzymatic synthesis of N-(purin-6-ylcarbamoyl)threonine, an anticodon-adjacent base in transfer ribonucleic acid","volume":"13","author":"Elkins","year":"1974","journal-title":"Biochemistry"},{"key":"2021110312483238100_B81","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/prot.21794","article-title":"X-ray crystal structure of a hypothetical Sua5 protein from Sulfolobus tokodaii strain 7","volume":"70","author":"Agari","year":"2008","journal-title":"Proteins"},{"key":"2021110312483238100_B82","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1038\/emboj.2009.92","article-title":"Sua5p a single-stranded telomeric DNA-binding protein facilitates telomere replication","volume":"28","author":"Meng","year":"2009","journal-title":"EMBO J."},{"key":"2021110312483238100_B83","doi-asserted-by":"crossref","first-page":"8950","DOI":"10.1021\/bi301233d","article-title":"Mechanism of N6-threonylcarbamoyladenonsine (t(6)A) biosynthesis: isolation and characterization of the intermediate threonylcarbamoyl-AMP","volume":"51","author":"Lauhon","year":"2012","journal-title":"Biochemistry"},{"key":"2021110312483238100_B84","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1093\/nar\/gkab026","article-title":"Structure of a reaction intermediate mimic in t6A biosynthesis bound in the active site of the TsaBD heterodimer from Escherichia coli","volume":"49","author":"Kopina","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B85","doi-asserted-by":"crossref","first-page":"20032","DOI":"10.1074\/jbc.M114.631242","article-title":"NMR-based Structural Analysis of Threonylcarbamoyl-AMP Synthase and Its Substrate Interactions","volume":"290","author":"Harris","year":"2015","journal-title":"J. Biol. Chem."},{"key":"2021110312483238100_B86","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1002\/prot.23026","article-title":"Crystal structure of Sulfolobus tokodaii Sua5 complexed with L-threonine and AMPPNP","volume":"79","author":"Kuratani","year":"2011","journal-title":"Proteins"},{"key":"2021110312483238100_B87","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1261\/rna.066092.118","article-title":"Structure-function analysis of Sua5 protein reveals novel functional motifs required for the biosynthesis of the universal t(6)A tRNA modification","volume":"24","author":"Pichard-Kostuch","year":"2018","journal-title":"RNA"},{"key":"2021110312483238100_B88","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1002\/anie.201108896","article-title":"The O-carbamoyltransferase TobZ catalyzes an ancient enzymatic reaction","volume":"51","author":"Parthier","year":"2012","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"2021110312483238100_B89","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.1093\/nar\/gkaa093","article-title":"Molecular basis for t6A modification in human mitochondria","volume":"48","author":"Zhou","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B90","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/prot.20982","article-title":"Structural characterization of Salmonella typhimurium YeaZ, an M22 O-sialoglycoprotein endopeptidase homolog","volume":"64","author":"Nichols","year":"2006","journal-title":"Proteins"},{"key":"2021110312483238100_B91","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/pro.2247","article-title":"Crystal structure of the dimer of two essential Salmonella typhimurium proteins, YgjD & YeaZ and calorimetric evidence for the formation of a ternary YgjD-YeaZ-YjeE complex","volume":"22","author":"Nichols","year":"2013","journal-title":"Protein Sci."},{"key":"2021110312483238100_B92","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1093\/nar\/gku1397","article-title":"The ATP-mediated formation of the YgjD-YeaZ-YjeE complex is required for the biosynthesis of tRNA t6A in Escherichia coli","volume":"43","author":"Zhang","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B93","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1093\/nar\/gkx1300","article-title":"Structure and mechanism of a bacterial t6A biosynthesis system","volume":"46","author":"Luthra","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B94","doi-asserted-by":"crossref","first-page":"5850","DOI":"10.1093\/nar\/gky323","article-title":"The structure of the TsaB\/TsaD\/TsaE complex reveals an unexpected mechanism for the bacterial t6A tRNA-modification","volume":"46","author":"Missoury","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B95","doi-asserted-by":"crossref","first-page":"6551","DOI":"10.1093\/nar\/gkz439","article-title":"Conformational communication mediates the reset step in t6A biosynthesis","volume":"47","author":"Luthra","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B96","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1261\/rna.075747.120","article-title":"Specificity in the biosynthesis of the universal tRNA nucleoside N (6)-threonylcarbamoyl adenosine (t(6)A)-TsaD is the gatekeeper","volume":"26","author":"Swinehart","year":"2020","journal-title":"RNA"},{"key":"2021110312483238100_B97","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1261\/rna.077537.120","article-title":"Comparative patterns of modified nucleotides in individual tRNA species from a mesophilic and two thermophilic archaea","volume":"26","author":"Wolff","year":"2020","journal-title":"RNA"},{"key":"2021110312483238100_B98","doi-asserted-by":"crossref","first-page":"e00690-18","DOI":"10.1128\/JB.00690-18","article-title":"tRNA Modification Profiles and Codon-Decoding Strategies in Methanocaldococcus jannaschii","volume":"201","author":"Yu","year":"2019","journal-title":"J. Bacteriol."},{"key":"2021110312483238100_B99","doi-asserted-by":"crossref","first-page":"3358","DOI":"10.1093\/nar\/gkv155","article-title":"Crystal structures of the Gon7\/Pcc1 and Bud32\/Cgi121 complexes provide a model for the complete yeast KEOPS complex","volume":"43","author":"Zhang","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B100","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.cell.2005.06.044","article-title":"Higher-order substrate recognition of eIF2alpha by the RNA-dependent protein kinase PKR","volume":"122","author":"Dar","year":"2005","journal-title":"Cell"},{"key":"2021110312483238100_B101","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s42003-021-01683-4","article-title":"Crystal structure of the human PRPK-TPRKB complex","volume":"4","author":"Li","year":"2021","journal-title":"Commun Biol"},{"key":"2021110312483238100_B102","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.1038\/s41467-020-19990-5","article-title":"A substrate binding model for the KEOPS tRNA modifying complex","volume":"11","author":"Beenstock","year":"2020","journal-title":"Nat. Commun."},{"key":"2021110312483238100_B103","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1146\/annurev.bb.25.060196.001033","article-title":"The sugar kinase\/heat shock protein 70\/actin superfamily: implications of conserved structure for mechanism","volume":"25","author":"Hurley","year":"1996","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"2021110312483238100_B104","doi-asserted-by":"crossref","first-page":"6042","DOI":"10.1093\/nar\/gkm554","article-title":"An archaeal orthologue of the universal protein Kae1 is an iron metalloprotein which exhibits atypical DNA-binding properties and apurinic-endonuclease activity in vitro","volume":"35","author":"Hecker","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B105","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1107\/S2053230X14014046","article-title":"Structure of Saccharomyces cerevisiae mitochondrial Qri7 in complex with AMP","volume":"70","author":"Tominaga","year":"2014","journal-title":"Acta Crystallogr. F Struct. Biol. Commun"},{"key":"2021110312483238100_B106","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1038\/s41467-018-04250-4","article-title":"CO2-sensitive tRNA modification associated with human mitochondrial disease","volume":"9","author":"Lin","year":"2018","journal-title":"Nat. Commun."},{"key":"2021110312483238100_B107","first-page":"24","article-title":"Structural requirements for enzymatic formation of threonylcarbamoyladenosine (t6A) in tRNA: an in vivo study with Xenopus laevis oocytes","volume":"4","author":"Morin","year":"1998","journal-title":"RNA"},{"key":"2021110312483238100_B108","doi-asserted-by":"crossref","first-page":"4662","DOI":"10.1093\/nar\/gky243","article-title":"A natural non-Watson-Crick base pair in human mitochondrial tRNAThr causes structural and functional susceptibility to local mutations","volume":"46","author":"Wang","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B109","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1093\/nar\/gkw1181","article-title":"Proteomic analysis of the human KEOPS complex identifies C14ORF142 as a core subunit homologous to yeast Gon7","volume":"45","author":"Wan","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B110","doi-asserted-by":"crossref","first-page":"6971","DOI":"10.1093\/nar\/gkw542","article-title":"Structural and functional characterization of KEOPS dimerization by Pcc1 and its role in t6A biosynthesis","volume":"44","author":"Wan","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2021110312483238100_B111","doi-asserted-by":"crossref","first-page":"e42822","DOI":"10.1371\/journal.pone.0042822","article-title":"The human EKC\/KEOPS complex is recruited to Cullin2 ubiquitin ligases by the human tumour antigen PRAME","volume":"7","author":"Costessi","year":"2012","journal-title":"PLoS One"},{"key":"2021110312483238100_B112","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/376313a0","article-title":"Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex","volume":"376","author":"Jeffrey","year":"1995","journal-title":"Nature"},{"key":"2021110312483238100_B113","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1146\/annurev.biochem.69.1.617","article-title":"Aminoacyl-tRNA synthesis","volume":"69","author":"Ibba","year":"2000","journal-title":"Annu. Rev. Biochem."},{"key":"2021110312483238100_B114","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41594-019-0211-4","article-title":"Mechanism for recycling tRNAs on stalled ribosomes","volume":"26","author":"Yip","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2021110312483238100_B115","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1126\/science.1213671","article-title":"tRNAs marked with CCACCA are targeted for degradation","volume":"334","author":"Wilusz","year":"2011","journal-title":"Science"},{"key":"2021110312483238100_B116","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.molcel.2007.09.021","article-title":"Trm9-catalyzed tRNA modifications link translation to the DNA damage response","volume":"28","author":"Begley","year":"2007","journal-title":"Mol. 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USA"},{"key":"2021110312483238100_B120","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.1016\/j.febslet.2014.09.038","article-title":"tRNA modifications regulate translation during cellular stress","volume":"588","author":"Gu","year":"2014","journal-title":"FEBS Lett."},{"key":"2021110312483238100_B121","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nature02046","article-title":"Global analysis of protein expression in yeast","volume":"425","author":"Ghaemmaghami","year":"2003","journal-title":"Nature"},{"key":"2021110312483238100_B122","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1042\/EBC20170102","article-title":"Mitochondrial transcription and translation: overview","volume":"62","author":"D'Souza","year":"2018","journal-title":"Essays Biochem."},{"key":"2021110312483238100_B123","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1038\/s41467-020-18068-6","article-title":"Complete chemical structures of human mitochondrial tRNAs","volume":"11","author":"Suzuki","year":"2020","journal-title":"Nat. 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