Santra, Mantu and Bagchi, Biman (2013) Kinetic proofreading at single molecular level: aminoacylation of tRNA(Ile) and the role of water as an editor. In: PLOS One, 8 (6). 0066112_1-0066112_9.
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Abstract
Proofreading/editing in protein synthesis is essential for accurate translation of information from the genetic code. In this article we present a theoretical investigation of efficiency of a kinetic proofreading mechanism that employs hydrolysis of the wrong substrate as the discriminatory step in enzyme catalytic reactions. We consider aminoacylation of tRNA(Ile) which is a crucial step in protein synthesis and for which experimental results are now available. We present an augmented kinetic scheme and then employ methods of stochastic simulation algorithm to obtain time dependent concentrations of different substances involved in the reaction and their rates of formation. We obtain the rates of product formation and ATP hydrolysis for both correct and wrong substrates (isoleucine and valine in our case, respectively), in single molecular enzyme as well as ensemble enzyme kinetics. The present theoretical scheme correctly reproduces (i) the amplitude of the discrimination factor in the overall rates between isoleucine and valine which is obtained as (1.8x10(2)).(4.33x10(2)) = 7.8x10(4), (ii) the rates of ATP hydrolysis for both Ile and Val at different substrate concentrations in the aminoacylation of tRNA(Ile). The present study shows a non-michaelis type dependence of rate of reaction on tRNA(Ile) concentration in case of valine. The overall editing in steady state is found to be independent of amino acid concentration. Interestingly, the computed ATP hydrolysis rate for valine at high substrate concentration is same as the rate of formation of Ile-tRNA(Ile) whereas at intermediate substrate concentration the ATP hydrolysis rate is relatively low. We find that the presence of additional editing domain in class I editing enzyme makes the kinetic proofreading more efficient through enhanced hydrolysis of wrong product at the editing CP1 domain.
| Item Type: | Journal Article |
|---|---|
| Publication: | PLOS One |
| Publisher: | Public Library of Science |
| Additional Information: | Copyright of this article belongs to Public Library of Science. |
| Department/Centre: | Division of Chemical Sciences > Solid State & Structural Chemistry Unit |
| Date Deposited: | 01 Oct 2013 11:36 |
| Last Modified: | 01 Oct 2013 11:36 |
| URI: | http://eprints.iisc.ac.in/id/eprint/47446 |
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