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The Conformation of a Catalytic Loop Is Central to GTPase Activity on the Ribosome
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
2015 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 54, no 2, 546-556 p.Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
2015. Vol. 54, no 2, 546-556 p.
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:uu:diva-247161DOI: 10.1021/bi501373gISI: 000348333300043PubMedID: 25515218OAI: oai:DiVA.org:uu-247161DiVA: diva2:795525
Swedish National Infrastructure for Computing (SNIC), 2013/26-1
Available from: 2015-03-16 Created: 2015-03-13 Last updated: 2016-04-07

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Åqvist, JohanKamerlin, Lynn Shina Caroline
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