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. 1980 Sep;31(3):333–358. doi: 10.1016/S0006-3495(80)85063-6

Thermodynamic constraints on kinetic proofreading in biosynthetic pathways.

M Ehrenberg, C Blomberg
PMCID: PMC1328794  PMID: 7260292

Abstract

We develop a quantitative theory of kinetic proofreading with an arbitrary number of checking steps after the hydrolysis of a nucleoside triphosphate. In particular, we investigate the relationship between the minimum dissipation of free energy required for a given error frequency in such systems. Several conclusions can be drawn from the present treatment: first, the ultimate accuracy of error correcting selective pathways is set by the displacement from equilibrium of the nucleoside triphosphates. Second, it is advantageous to achieve a desired accuracy at a small energy dissipation with several checking steps rather than a single one. This could explain antinomies in the amino acylation reaction as well as in mRNA translation, where small structural differences lead to large differences in flow rates between right and wrong substrates. Third, all checking steps should contribute equally to the accuracy, which implies a specific and symmetrical set of rate constants for the checking events on the enzyme.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baldwin A. N., Berg P. Transfer ribonucleic acid-induced hydrolysis of valyladenylate bound to isoleucyl ribonucleic acid synthetase. J Biol Chem. 1966 Feb 25;241(4):839–845. [PubMed] [Google Scholar]
  2. Brutlag D., Kornberg A. Enzymatic synthesis of deoxyribonucleic acid. 36. A proofreading function for the 3' leads to 5' exonuclease activity in deoxyribonucleic acid polymerases. J Biol Chem. 1972 Jan 10;247(1):241–248. [PubMed] [Google Scholar]
  3. Fersht A. R., Dingwall C. Establishing the misacylation/deacylation of the tRNA pathway for the editing mechanism of prokaryotic and eukaryotic valyl-tRNA synthetases. Biochemistry. 1979 Apr 3;18(7):1238–1245. doi: 10.1021/bi00574a019. [DOI] [PubMed] [Google Scholar]
  4. Fersht A. R. Editing mechanisms in protein synthesis. Rejection of valine by the isoleucyl-tRNA synthetase. Biochemistry. 1977 Mar 8;16(5):1025–1030. doi: 10.1021/bi00624a034. [DOI] [PubMed] [Google Scholar]
  5. Fersht A. R., Kaethner M. M. Enzyme hyperspecificity. Rejection of threonine by the valyl-tRNA synthetase by misacylation and hydrolytic editing. Biochemistry. 1976 Jul 27;15(15):3342–3346. doi: 10.1021/bi00660a026. [DOI] [PubMed] [Google Scholar]
  6. Fowler R. G., Degnen G. E., Cox E. C. Mutational specificity of a conditional Escherichia coli mutator, mutD5. Mol Gen Genet. 1974;133(3):179–191. doi: 10.1007/BF00267667. [DOI] [PubMed] [Google Scholar]
  7. Galas D. J., Branscomb E. W. Enzymatic determinants of DNA polymerase accuracy. Theory of coliphage T4 polymerase mechanisms. J Mol Biol. 1978 Oct 5;124(4):653–687. doi: 10.1016/0022-2836(78)90176-6. [DOI] [PubMed] [Google Scholar]
  8. Goulian M., Lucas Z. J., Kornberg A. Enzymatic synthesis of deoxyribonucleic acid. XXV. Purification and properties of deoxyribonucleic acid polymerase induced by infection with phage T4. J Biol Chem. 1968 Feb 10;243(3):627–638. [PubMed] [Google Scholar]
  9. Grosjean H. J., de Henau S., Crothers D. M. On the physical basis for ambiguity in genetic coding interactions. Proc Natl Acad Sci U S A. 1978 Feb;75(2):610–614. doi: 10.1073/pnas.75.2.610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hopfield J. J. Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4135–4139. doi: 10.1073/pnas.71.10.4135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jovin T. M., Englund P. T., Kornberg A. Enzymatic synthesis of deoxyribonucleic acid. XXVII. Chemical modifications of deoxyribonucleic acid polymerase. J Biol Chem. 1969 Jun 10;244(11):3009–3018. [PubMed] [Google Scholar]
  12. Kornberg A. Active center of DNA polymerase. Science. 1969 Mar 28;163(3874):1410–1418. doi: 10.1126/science.163.3874.1410. [DOI] [PubMed] [Google Scholar]
  13. Kurland C. G., Rigler R., Ehrenberg M., Blomberg C. Allosteric mechanism for codon-dependent tRNA selection on ribosomes. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4248–4251. doi: 10.1073/pnas.72.11.4248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kurland C. G. The role of guanine nucleotides in protein biosynthesis. Biophys J. 1978 Jun;22(3):373–392. doi: 10.1016/S0006-3495(78)85494-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. LOFTFIELD R. B. THE FREQUENCY OF ERRORS IN PROTEIN BIOSYNTHESIS. Biochem J. 1963 Oct;89:82–92. doi: 10.1042/bj0890082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Loftfield R. B., Vanderjagt D. The frequency of errors in protein biosynthesis. Biochem J. 1972 Aug;128(5):1353–1356. doi: 10.1042/bj1281353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mulvey R. S., Fersht A. R. Editing mechanisms in aminoacylation of tRNA: ATP consumption and the binding of aminoacyl-tRNA by elongation factor Tu. Biochemistry. 1977 Oct 18;16(21):4731–4737. doi: 10.1021/bi00640a031. [DOI] [PubMed] [Google Scholar]
  18. NORRIS A. T., BERG P. MECHANISM OF AMINOACYL RNA SYNTHESIS: STUDIES WITH ISOLATED AMINOACYL ADENYLATE COMPLEXES OF ISOLEUCYL RNA SYNTHETASE. Proc Natl Acad Sci U S A. 1964 Aug;52:330–337. doi: 10.1073/pnas.52.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ninio J. Kinetic amplification of enzyme discrimination. Biochimie. 1975;57(5):587–595. doi: 10.1016/s0300-9084(75)80139-8. [DOI] [PubMed] [Google Scholar]
  20. Savageau M. A., Freter R. R. Energy cost of proofreading to increase fidelity of transfer ribonucleic acid aminoacylation. Biochemistry. 1979 Aug 7;18(16):3486–3493. doi: 10.1021/bi00583a008. [DOI] [PubMed] [Google Scholar]

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