Proofreading kinetic

J. J. Hopfield has suggested a general mechanism called kinetic proofreading in which there is no hydrolytic site on the enzyme instead, the desired intermediates diffuse into solution, where they hydrolyze nonenzymatically.54 An example is in the selection of amino acids by the aminoacyl-tRNA synthetases (equation 13.32). 

J. J. Hopfield has proposed a so-called energy relay model [101], in which the ping-pong mechanism operates on two identical substrate molecules and releases two identical product molecules. The model introduces the novel idea of dynamic cooperativity by which biomolecular processes in living cells, such as DNA replication and protein biosynthesis, can achieve high fidelity. The model was developed as an alternative to the kinetic proofreading mechanism which we shall discuss in Chapter 5. 

J. J. Hopfield. Kinetic proofreading a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc. Natl. Acad. Sci. USA, 71 4135 1139, 1974. 

Both the prokaryotic and the eukaryotic excision nucleases employ thermodynamic discrimination and kinetic proofreading to achieve high specificity. However, despite these elaborate discriminatory mechanisms, excision nucleases do not have absolute specificity and gratuitous repair of undamaged DNA occurs at a low but potentially deleterious level (23-25). 

Blanchard SC, Gonzalez RL, Kim HD, Chu S, Puglisi JD. tRNA selection and kinetic proofreading in translation. Nat. Struct. Mol. Biol. 2004 11 1008-1014. 

Okamoto, M. Savageau, M. A. (1984). Integrated function of a kinetic proofreading mechanism steady-state analysis testing internal consistency of data obtained in vivo and in vitro and predicting parameter values. Biochemistry 23,1701-1709. 

In conclusion, the biochemical properties of the APIase function of hsp70 molecular chaperones allow kinetic proofreading of folding by rapid scanning of APIase-sensitive sites of unfolded polypeptide chains. 

Kinetic proofreading is a mechanism that ensures that the correct codon-anticodon pairing occurs in the A site of ribosomes. In eukaryotes eEF-la mediates the binding of aminoacyl-tRNAs to the A site. When the correct pairing occurs eEF-1 a hydrolyses its bound GTP and subsequently exits the ribosome. 

T.W. McKeithan, Kinetic proofreading in T-cell receptor signal transduction, Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 5042-5046. 

B. Goldstein, Kinetic proofreading in receptor-mediated transduction of cellular signals receptor aggregation, partially activated receptors, and cytosolic messengers, Bull. Math. Biol. 2002, 64, 887-911. 

The tRNA selection pathway and kinetic proofreading. Aminoacyl-tRNA is delivered to the ribosomal A-site as a ternary complex with elongation factor EF-Tu and GTP. The events between the initial binding of the ternary complex and the incorporation of the amino acid into the peptide have been dissected into several kineti-cally distinguishable steps, as shown in Figure 13.17. 

MacGlashan, D. (2001). Signaling cascades escape from kinetic proofreading. Froc. Natl. Acad. Sci. USA 98, 6989-6990. 

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