{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T06:18:47Z","timestamp":1783750727997,"version":"3.55.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020","doi-asserted-by":"publisher","award":["764591"],"award-info":[{"award-number":["764591"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In translation, G\u2022U mismatch in codon-anticodon decoding is an error hotspot likely due to transition of G\u2022U from wobble (wb) to Watson-Crick (WC) geometry, which is governed by keto\/enol tautomerization (wb-WC reaction). Yet, effects of the ribosome on the wb-WC reaction and its implications for decoding mechanism remain unclear. Employing quantum-mechanical\/molecular-mechanical umbrella sampling simulations using models of the ribosomal decoding site (A site) we determined that the wb-WC reaction is endoergic in the open, but weakly exoergic in the closed A-site state. We extended the classical \u2018induced-fit\u2019 model of initial selection by incorporating wb-WC reaction parameters in open and closed states. For predicted parameters, the non-equilibrium exoergic wb-WC reaction is kinetically limited by the decoding rates. The model explains early observations of the WC geometry of G\u2022U from equilibrium structural studies and reveals discrimination capacity for the working ribosome operating at non-equilibrium conditions. The equilibration of the exoergic wb-WC reaction counteracts the equilibration of the open-closed transition of the A site, constraining the decoding accuracy and potentially explaining the persistence of the G\u2022U as an error hotspot. Our results unify structural and mechanistic views of codon-anticodon decoding and generalize the \u2018induced-fit\u2019 model for flexible substrates.<\/jats:p>","DOI":"10.1093\/nar\/gkab947","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T17:47:54Z","timestamp":1633110474000},"page":"11823-11833","source":"Crossref","is-referenced-by-count":8,"title":["Constraints on error rate revealed by computational study of G\u2022U tautomerization in translation"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7587-9983","authenticated-orcid":false,"given":"Andriy","family":"Kazantsev","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Department of Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9478-8825","authenticated-orcid":false,"given":"Zoya","family":"Ignatova","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Department of Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"2021111805153463800_B1","first-page":"773","article-title":"Codon misreading tRNAs promote tumor growth in mice","volume":"15","author":"Santos","year":"2018","journal-title":"RNA Biol."},{"key":"2021111805153463800_B2","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1111\/acel.12628","article-title":"Translation fidelity coevolves with longevity","volume":"16","author":"Ke","year":"2017","journal-title":"Aging Cell"},{"key":"2021111805153463800_B3","doi-asserted-by":"crossref","first-page":"6170","DOI":"10.1093\/nar\/gkaa221","article-title":"The nature of the purine at position 34 in tRNAs of 4-codon boxes is correlated with nucleotides at positions 32 and 38 to maintain decoding fidelity","volume":"48","author":"Pernod","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2021111805153463800_B4","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1093\/nar\/gky1319","article-title":"Broad range of missense error frequencies in cellular proteins","volume":"47","author":"Garofalo","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2021111805153463800_B5","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.molcel.2019.06.041","article-title":"Systematic detection of amino acid substitutions in proteomes reveals mechanistic basis of ribosome errors and selection for translation fidelity","volume":"75","author":"Mordret","year":"2019","journal-title":"Mol. 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