Peptide bond formation does not involve acid-base catalysis by ribosomal residues

Nature Structural & Molecular Biology
Peter BielingM V Rodnina

Abstract

Ribosomes catalyze the formation of peptide bonds between aminoacyl esters of transfer RNAs within a catalytic center composed of ribosomal RNA only. Here we show that the reaction of P-site formylmethionine (fMet)-tRNA(fMet) with a modified A-site tRNA substrate, Phelac-tRNA(Phe), in which the nucleophilic amino group is replaced with a hydroxyl group, does not show the pH dependence observed with small substrate analogs such as puromycin and hydroxypuromycin. This indicates that acid-base catalysis by ribosomal residues is not important in the reaction with the full-size substrate. Rather, the ribosome catalyzes peptide bond formation by positioning the tRNAs, or their 3' termini, through interactions with rRNA that induce and/or stabilize a pH-insensitive conformation of the active site and provide a preorganized environment facilitating the reaction. The rate of peptide bond formation with unmodified Phe-tRNA(Phe) is estimated to be >300 s(-1).

References

Oct 30, 1974·Journal of the American Chemical Society·A C Satterthwait, W P Jencks
Jan 1, 1974·Methods in Enzymology·S FahnestockA Rich
Jun 9, 1970·Biochemistry·S FahnestockA Rich
Jan 6, 1971·Nature: New Biology·S Fahnestock, A Rich
Mar 25, 1982·Journal of Molecular Biology·A E JohnsonC R Cantor
Jan 10, 1983·FEBS Letters·K H Derwenskus, M Sprinzl
Jan 6, 1995·Science·A Radzicka, R Wolfenden
Mar 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·M V Rodnina, W Wintermeyer
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·M V RodninaW Wintermeyer
Jan 5, 2000·Molecular Cell·D F Kim, R Green
Apr 3, 2001·Science·M M YusupovH F Noller
Jun 8, 2001·Annual Review of Biochemistry·M V Rodnina, W Wintermeyer
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·M A BayfieldA Barta
Aug 20, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey L HansenThomas A Steitz
Sep 1, 1963·Biochemistry·R WOLFENDEN
Dec 24, 2003·Biopolymers·Philip C BevilacquaRieko Yajima
May 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Annette SieversRichard Wolfenden
Oct 12, 2004·Nature Structural & Molecular Biology·Joshua S WeingerScott A Strobel
Mar 9, 2005·Biochemistry·Amy C SeilaScott A Strobel
Jun 16, 2005·Nature Reviews. Molecular Cell Biology·Martha J Fedor, James R Williamson
Aug 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Stefan Trobro, Johan Aqvist
Sep 1, 2005·The Journal of Biological Chemistry·Malte BeringerMarina V Rodnina

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Citations

Nov 26, 2011·Journal of Biosciences·Koji Tamura
Oct 25, 2006·Biochemistry·S A AdediranR F Pratt
Jan 26, 2008·Molecular Pharmaceutics·Elizabeth A FelnagleMichael G Thomas
Jul 19, 2011·Nature·David A HillerScott A Strobel
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Göran Wallin, Johan Aqvist
May 2, 2008·The Journal of Biological Chemistry·Dongli PanBarry S Cooperman
Apr 21, 2009·Nucleic Acids Research·Anthony C Forster
Aug 7, 2009·Journal of the Royal Society, Interface·Ada Yonath
Jun 12, 2008·Annual Review of Microbiology·Elaine M YoungmanRachel Green
Mar 6, 2012·BMC Bioinformatics·Mohd Firdaus-RaihPeter J Artymiuk
Jun 12, 2013·Annual Review of Biochemistry·Rebecca M Voorhees, V Ramakrishnan
May 10, 2011·Annual Review of Biochemistry·Edward Ki Yun LeungJoseph Anthony Piccirilli
Dec 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Magnus JohanssonMåns Ehrenberg
Oct 28, 2014·ELife·Justin GardinBruce Futcher
May 29, 2013·Current Opinion in Structural Biology·Marina V Rodnina
Aug 14, 2012·Current Opinion in Structural Biology·Johan AqvistGöran Wallin
Jul 15, 2009·Biochimica Et Biophysica Acta·Miljan Simonović, Thomas A Steitz
Jun 13, 2008·Trends in Microbiology·Anat Bashan, Ada Yonath
Sep 22, 2007·Current Opinion in Chemical Biology·Masaki OhuchiHiroaki Suga
Dec 13, 2006·Trends in Biochemical Sciences·Marina V RodninaWolfgang Wintermeyer
Jun 27, 2006·EMBO Reports·Ingo WohlgemuthMarina V Rodnina
Sep 16, 2010·The EMBO Journal·Ingo WohlgemuthMarina V Rodnina
Jun 10, 2008·Molecular Cell·Magnus JohanssonMåns Ehrenberg
May 15, 2007·Molecular Cell·Malte Beringer, Marina V Rodnina
Dec 23, 2008·Journal of Molecular Biology·Takatsugu KobayashiShigeyuki Yokoyama
Dec 22, 2007·Chemistry & Biology·Atsushi OhtaHiroaki Suga
Jul 11, 2008·Molecular Cell·Sarah Ledoux, Olke C Uhlenbeck
Feb 1, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Michael Y PavlovMåns Ehrenberg

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