The conformation of a catalytic loop is central to GTPase activity on the ribosome.

作者: Johan Åqvist , Shina C. L. Kamerlin

DOI: 10.1021/BI501373G

关键词: BiochemistryGTPaseConformational changeBiophysicsProtein biosynthesisGTP'HistidineRibosomeLarge ribosomal subunitEnzymeBiology

摘要: The translational GTPases hydrolyze GTP on the ribosome at several stages of protein synthesis cycle. Because strong conservation their catalytic center, these enzymes are expected to operate through a universal hydrolysis mechanism, in which critical histidine residue together with sarcin–ricin loop large ribosomal subunit is necessary for GTPase activation. Here we examine different possible pathways by EF-Tu extensive computer simulations. We show that conformational change peptide plane preceding this has decisive effect energetics reaction. This transition was predicted earlier us and recently been confirmed experimentally. It found promote early proton transfer from water γ-phosphate group GTP, followed nucleophilic attack hydroxide ion. calculated reaction good agreement available kinetic data, both wild-type mutant versions EF-Tu, indicates ...

参考文章(44)
Rolf Hilgenfeld, Jeroen Mesters, Tanis Hogg, Insights into the GTPase Mechanism of EF-Tu from Structural Studies The Ribosome: Structure, Function, Antibiotics, and Cellular Interactions. ,vol. 28, pp. 347- 357 ,(2000) , 10.1128/9781555818142.CH28
Göran Wallin, Shina C. L. Kamerlin, Johan Åqvist, Energetics of activation of GTP hydrolysis on the ribosome. Nature Communications. ,vol. 4, pp. 1733- ,(2013) , 10.1038/NCOMMS2741
Gregory King, Arieh Warshel, A surface constrained all‐atom solvent model for effective simulations of polar solutions Journal of Chemical Physics. ,vol. 91, pp. 3647- 3661 ,(1989) , 10.1063/1.456845
Frederick S. Lee, Arieh Warshel, A local reaction field method for fast evaluation of long‐range electrostatic interactions in molecular simulations Journal of Chemical Physics. ,vol. 97, pp. 3100- 3107 ,(1992) , 10.1063/1.462997
David S. Tourigny, Israel S. Fernández, Ann C. Kelley, V. Ramakrishnan, Elongation factor G bound to the ribosome in an intermediate state of translocation. Science. ,vol. 340, pp. 1235490- 1235490 ,(2013) , 10.1126/SCIENCE.1235490
Klaus Scheffzek, Mohammad Reza Ahmadian, Wolfgang Kabsch, Lisa Wiesmuller, Alfred Lautwein, Frank Schmitz, Alfred Wittinghofer, The Ras-RasGAP Complex: Structural Basis for GTPase Activation and Its Loss in Oncogenic Ras Mutants Science. ,vol. 277, pp. 333- 338 ,(1997) , 10.1126/SCIENCE.277.5324.333
R. J. Read, Improved Fourier coefficients for maps using phases from partial structures with errors Acta Crystallographica Section A. ,vol. 42, pp. 140- 149 ,(1986) , 10.1107/S0108767386099622
Marco Klähn, Edina Rosta, Arieh Warshel, On the Mechanism of Hydrolysis of Phosphate Monoesters Dianions in Solutions and Proteins Journal of the American Chemical Society. ,vol. 128, pp. 15310- 15323 ,(2006) , 10.1021/JA065470T