Exceptionally large entropy contributions enable the high rates of GTP hydrolysis on the ribosome
Åqvist, Johan and Kamerlin, Shina C L LU
(2015)
In Scientific Reports
5.
- Abstract
Protein synthesis on the ribosome involves hydrolysis of GTP in several key steps of the mRNA translation cycle. These steps are catalyzed by the translational GTPases of which elongation factor Tu (EF-Tu) is the fastest GTPase known. Here, we use extensive computer simulations to explore the origin of its remarkably high catalytic rate on the ribosome and show that it is made possible by a very large positive activation entropy. This entropy term (TΔS(‡)) amounts to more than 7 kcal/mol at 25 °C. It is further found to be characteristic of the reaction mechanism utilized by the translational, but not other, GTPases and it enables these enzymes to attain hydrolysis rates exceeding 500 s(-1). This entropy driven mechanism likely reflects... (More)
Protein synthesis on the ribosome involves hydrolysis of GTP in several key steps of the mRNA translation cycle. These steps are catalyzed by the translational GTPases of which elongation factor Tu (EF-Tu) is the fastest GTPase known. Here, we use extensive computer simulations to explore the origin of its remarkably high catalytic rate on the ribosome and show that it is made possible by a very large positive activation entropy. This entropy term (TΔS(‡)) amounts to more than 7 kcal/mol at 25 °C. It is further found to be characteristic of the reaction mechanism utilized by the translational, but not other, GTPases and it enables these enzymes to attain hydrolysis rates exceeding 500 s(-1). This entropy driven mechanism likely reflects the very high selection pressure on the speed of protein synthesis, which drives the rate of each individual GTPase towards maximal turnover rate of the whole translation cycle.
(Less)
- author
- Åqvist, Johan
and Kamerlin, Shina C L
LU
- publishing date
- 2015-10-26
- type
- Contribution to journal
- publication status
- published
- keywords
- Biocatalysis, Catalytic Domain, Entropy, Guanosine Triphosphate/metabolism, Hydrolysis, Kinetics, Molecular Dynamics Simulation, Peptide Elongation Factor Tu/chemistry, Ribosomes/chemistry, Temperature
- in
- Scientific Reports
- volume
- 5
- article number
- 15817
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:84945252253
- pmid:26497916
- ISSN
- 2045-2322
- DOI
- 10.1038/srep15817
- language
- English
- LU publication?
- no
- id
- d81777b6-e6aa-4e6a-9ee3-6530b218e906
- date added to LUP
- 2025-01-11 21:35:40
- date last changed
- 2025-04-20 11:52:42
@article{d81777b6-e6aa-4e6a-9ee3-6530b218e906,
abstract = {{<p>Protein synthesis on the ribosome involves hydrolysis of GTP in several key steps of the mRNA translation cycle. These steps are catalyzed by the translational GTPases of which elongation factor Tu (EF-Tu) is the fastest GTPase known. Here, we use extensive computer simulations to explore the origin of its remarkably high catalytic rate on the ribosome and show that it is made possible by a very large positive activation entropy. This entropy term (TΔS(‡)) amounts to more than 7 kcal/mol at 25 °C. It is further found to be characteristic of the reaction mechanism utilized by the translational, but not other, GTPases and it enables these enzymes to attain hydrolysis rates exceeding 500 s(-1). This entropy driven mechanism likely reflects the very high selection pressure on the speed of protein synthesis, which drives the rate of each individual GTPase towards maximal turnover rate of the whole translation cycle.</p>}},
author = {{Åqvist, Johan and Kamerlin, Shina C L}},
issn = {{2045-2322}},
keywords = {{Biocatalysis; Catalytic Domain; Entropy; Guanosine Triphosphate/metabolism; Hydrolysis; Kinetics; Molecular Dynamics Simulation; Peptide Elongation Factor Tu/chemistry; Ribosomes/chemistry; Temperature}},
language = {{eng}},
month = {{10}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Exceptionally large entropy contributions enable the high rates of GTP hydrolysis on the ribosome}},
url = {{http://dx.doi.org/10.1038/srep15817}},
doi = {{10.1038/srep15817}},
volume = {{5}},
year = {{2015}},
}