Browse by author
Lookup NU author(s): Dr Agata Starosta
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2015 American Chemical Society. The peptide bond formation with the amino acid proline (Pro) on the ribosome is slow, resulting in translational stalling when several Pro have to be incorporated into the peptide. Stalling at poly-Pro motifs is alleviated by the elongation factor P (EF-P). Here we investigate why Pro is a poor substrate and how EF-P catalyzes the reaction. Linear free energy relationships of the reaction on the ribosome and in solution using 12 different Pro analogues suggest that the positioning of Pro-tRNA in the peptidyl transferase center is the major determinant for the slow reaction. With any Pro analogue tested, EF-P decreases the activation energy of the reaction by an almost uniform value of 2.5 kcal/mol. The main source of catalysis is the favorable entropy change brought about by EF-P. Thus, EF-P acts by entropic steering of Pro-tRNA toward a catalytically productive orientation in the peptidyl transferase center of the ribosome.
Author(s): Doerfel LK, Wohlgemuth I, Kubyshkin V, Starosta AL, Wilson DN, Budisa N, Rodnina MV
Publication type: Article
Publication status: Published
Journal: Journal of the American Chemical Society
Year: 2015
Volume: 137
Issue: 40
Pages: 12997-13006
Online publication date: 18/09/2015
Acceptance date: 01/01/1900
ISSN (print): 0002-7863
ISSN (electronic): 1520-5126
Publisher: American Chemical Society
URL: http://doi.org/10.1021/jacs.5b07427
DOI: 10.1021/jacs.5b07427
PubMed id: 26384033
Altmetrics provided by Altmetric
