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pH-sensitivity of the ribosomal peptidyl transfer reaction dependent on the identity of the A-site aminoacyl-tRNA
Uppsala University.
Uppsala University.
Uppsala University.ORCID iD: 0000-0002-0468-9664
Frankrike.
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2011 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 1, p. 79-84Article in journal (Refereed) Published
Abstract [en]

We studied the pH-dependence of ribosome catalyzed peptidyl transfer from fMet-tRNA(fMet) to the aa-tRNAs Phe-tRNA(Phe), Ala-tRNA(Ala), Gly-tRNA(Gly), Pro-tRNA(Pro), Asn-tRNA(Asn), and Ile-tRNA(Ile), selected to cover a large range of intrinsic pK(a)-values for the α-amino group of their amino acids. The peptidyl transfer rates were different at pH 7.5 and displayed different pH-dependence, quantified as the pH-value, pK(a)(obs), at which the rate was half maximal. The pK(a)(obs)-values were downshifted relative to the intrinsic pK(a)-value of aa-tRNAs in bulk solution. Gly-tRNA(Gly) had the smallest downshift, while Ile-tRNA(Ile) and Ala-tRNA(Ala) had the largest downshifts. These downshifts correlate strongly with molecular dynamics (MD) estimates of the downshifts in pK(a)-values of these aa-tRNAs upon A-site binding. Our data show the chemistry of peptide bond formation to be rate limiting for peptidyl transfer at pH 7.5 in the Gly and Pro cases and indicate rate limiting chemistry for all six aa-tRNAs.

Place, publisher, year, edition, pages
2011. Vol. 108, no 1, p. 79-84
Keywords [en]
ribosome, kinetics, rate limiting step, accommodation, molecular dynamics
National Category
Theoretical Chemistry
Identifiers
URN: urn:nbn:se:hkr:diva-12009DOI: 10.1073/pnas.1012612107PubMedID: 21169502OAI: oai:DiVA.org:hkr-12009DiVA, id: diva2:719834
Available from: 2014-05-27 Created: 2014-05-27 Last updated: 2017-12-05Bibliographically approved

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Trobro, Stefan

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