Recognition: the Kinetic Concepts

  • J. Ninio
  • F. Chapeville
Part of the Molecular Biology, Biochemistry and Biophysics book series (MOLECULAR, volume 32)


Following Pauling’s analysis (Pauling 1948, 1958), most enzymologists relate enzyme specificity to the supposed geometric complementarity between enzyme and substrate, the structural match being realized either at the initial stage of binding or later during the formation of a transition complex (Koshland 1958; Wolfenden 1972; Fersht 1974; Jencks 1975). The concept of stereochemical complementarity (Fischer 1894), which is fundamental to our understanding of the replication of the genetic material (Pauling and Delbrück 1940; Watson and Crick 1953), was invoked whenever there was a problem of molecular specificity, from immunology (Ehrlich 1900; Haurowitz 1967) to molecular evolution (Woese 1967). Yet there is now a rapidly growing body of knowledge which is being produced and organized along a quite different mode of thinking. The following are a few examples of recent experimental findings which created difficulties for the geometric viewpoint and contributed to the spread of the kinetic ideas.


Geometric Viewpoint Kinetic Concept Cognate tRNA Translational Fidelity Transfer Ribonucleic Acid 
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  1. Allfrey VG, Faulkner R, Mirsky AE (1964) Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc Natl Acad Sci USA 51: 786–794PubMedCrossRefGoogle Scholar
  2. Apirion D, Phillips SL, Schlessinger D (1969) Approaches to the genetics of Escherichia coli ribosomes. Cold Spring Harb Symp Quant Biol 34: 117–128PubMedGoogle Scholar
  3. Baldwin AN, Berg P (1966) Transfer ribonucleic acid induced hydrolysis of valyladenylate bound to isoleucyl ribonucleic acid synthetase. J Biol Chem 241: 839–845PubMedGoogle Scholar
  4. Bell GI (1974) Model for the binding of multivalent antigen to cells. Nature 248: 430–431PubMedCrossRefGoogle Scholar
  5. Bernardi F, Ninio J (1978) The accuracy of DNA replication. Biochimie 60: 1083–1095PubMedCrossRefGoogle Scholar
  6. Bernardi F, Saghi M, Dorizzi M, Ninio J (1979) A new approach to DNA polymerase kinetics. J Mol Biol 129: 93–112PubMedCrossRefGoogle Scholar
  7. Bessman MJ, Muzyczka N, Goodman MF, Schnaar RL (1974) Studies on the biochemical basis of spontaneous mutation. III. The incorporation of a base and its analogue into DNA by wild-type, mutator and antimutator DNA polymerases. J Mol Biol 88: 409–421PubMedCrossRefGoogle Scholar
  8. Blomberg C (1977) A kinetic recognition process for tRNA at the ribosome. J Theor Biol 66: 307–325PubMedCrossRefGoogle Scholar
  9. Bonnet J, Giege R, Ebel J-P (1972) Lack of specificity in the amino-acyl-tRNA synthetase-catalysed deacylation of amino acyl-tRNA. FEBS Lett 27: 139–144PubMedCrossRefGoogle Scholar
  10. Brutlag D, Kornberg A (1972) Enzymatic synthesis of deoxyribonucleic acid. XXXVI. A proofreading function for the 3 → 5′ exonuclease activity in deoxyribonucleic acid polymerases. J Biol Chem 247: 241–248PubMedGoogle Scholar
  11. Caplan AB, Menninger JR (1979) Tests of the ribosomal editing hypothesis: amino acid starvation differentially enhances the dissociation of peptidyl-tRNAs from the ribosome. J Mol Biol 134: 621–637PubMedCrossRefGoogle Scholar
  12. Chapeville F, Yot P, Paulin D (1969) Enzymatic hydrolysis of N-acyl-aminoacyl transfer RNAs. Cold Spring Harb Symp Quant Biol 34: 493–498PubMedGoogle Scholar
  13. Chestier A, Yaniv M (1979) Rapid turnover of acetyl groups in the four core histones of simian virus 40 minichromosomes. Proc Natl Acad Sci USA 76: 46–50PubMedCrossRefGoogle Scholar
  14. Ehrlich P (1900) On immunity with special reference to cell life. Proc Roy Soc B 66: 424–448Google Scholar
  15. Eldred EW, Schimmel PR (1972) Rapid deacylation by isoleucyl transfer ribonucleic acid synthetase of isoleucine specific transfer ribonucleic acid aminoacylated with valine. J Biol Chem 247: 2961–2964PubMedGoogle Scholar
  16. Fersht AR (1974) Catalysis, binding and enzyme-substrate complementary. Proc R Soc London Ser B 187: 397–407CrossRefGoogle Scholar
  17. Fersht AR (1977) Enzyme structure and mechanism. Freeman, San Francisco Fersht AR, Kaethner MM (1976) Enzyme hyperspecificity. Rejection of threonine by the valyl-tRNA synthetase by misacylation and hydrolytic editing. Biochemistry 15: 3342–3346CrossRefGoogle Scholar
  18. Fischer E (1894) Einfluß der Configuration auf die Wirkung der Enzyme. Chem Ber 27: 2985–2993CrossRefGoogle Scholar
  19. Galas DJ, Branscomb EW (1976) Ribosome slowed by mutation to streptomycin resistance. Nature 262: 617–619PubMedCrossRefGoogle Scholar
  20. Galas DJ, Branscomb EW (1978) Enzymatic determinants of DNA polymerase accuracy. Theory of coliphage T4 polymerase mechanisms. J Mol Biol 124: 653–687PubMedCrossRefGoogle Scholar
  21. Gavrilova LP, Kostiashkina OE, Koteliansky VE, Rutkevitch NM, Spirin AS (1976) Factor-free (“non-enzymie”) and factor-dependent systems of translation of polyuridylic acid by Escherichia coli ribosomes. J Mol Biol 101: 537–552PubMedCrossRefGoogle Scholar
  22. Giegé R, Kern D, Ebel J-P, Grosjean H, de Henau S, Chantrenne H (1974) Incorrect aminoacylations involving tRNAs or valyl-tRNA synthetase from Bacillus stearothermophilus. Eur J Biochem 45: 351–362PubMedCrossRefGoogle Scholar
  23. Gorini L (1971) Ribosomal discrimination of tRNAs. Nature New Biol 234: 261–264 Guéron M (1978) Enhanced selectivity of enzymes by kinetic proofreading. Am Sci 66: 202–208Google Scholar
  24. Haar F von der, Cramer F (1976) Hydrolytic action of aminoacyl-tRNA synthetases from baker’s yeast: “chemical proofreading” preventing acylation of tRNAile with misactivated valine. Biochemistry 15: 4131–4138PubMedCrossRefGoogle Scholar
  25. Haurowitz F (1967) The evolution of selective and instructive theories of antibody formation. Cold Spring Harb Symp Quant Biol 32: 559–567Google Scholar
  26. Hershfield MS (1973) On the role of deoxyribonucleic acid polymerase in determining mutation rates. Characterization of the defect in the T4 deoxyribonucleic acid polymerase caused by the TS L88 mutation. J Biol Chem 248: 1417–1423PubMedGoogle Scholar
  27. Hippel PH von, Rezvin A, Gross CA, Wang AC (1974) Non-sepcific DNA binding of genome regulating proteins as a biological control mechanism: I. The lac Operon: equilibrium aspects. Proc Natl Acad Sci USA 71: 4808–4812CrossRefGoogle Scholar
  28. Hoffmann GW (1975) A theory of regulation and self-nonself discrimination in an immune network. Eur J Immunol 5: 638–647PubMedCrossRefGoogle Scholar
  29. Hopfield JJ (1974) Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc Natl Acad Sci USA 71: 4135–4139PubMedCrossRefGoogle Scholar
  30. Hopfield JJ, Yamane T, Yue V, Coutts SM (1976) Direct experimental evidence for kinetic proofreading in amino acylation of tRNAile. Proc Natl Acad Sci USA 73: 1164–1168PubMedCrossRefGoogle Scholar
  31. Igloi GL, von der Haar F, Cramer F (1977) Hydrolytic action of aminoacyl-tRNA synthetases from baker’s yeast: “chemical proofreading” of thr-tRNAval by valyl-tRNA synthetase studied with modified tRNAval and amino acid analogues. Biochemistry 16: 1696–1702PubMedCrossRefGoogle Scholar
  32. Inman JK (1978) The antibody combining region: speculations on the hypothesis of general multi-specificity. In: Bell GI, Perelson AJ, Good RA (eds) Theoretical immunology, pp 243–278. Dekker, New YorkGoogle Scholar
  33. Jelenc PC, Kurland CG (1979) Nucleoside triphosphate regeneration decreases the frequency of translation errors. Proc Natl Acad Sci USA 76: 3174–3178PubMedCrossRefGoogle Scholar
  34. Jencks WP (1975) Binding energy, specificity and enzyme catalysis: the Circe effect. Adv Enzymol 43: 219–410PubMedGoogle Scholar
  35. Jerne NK (1976) The immune system: a web of V-domains. The Harvey Lectures, Ser 70, pp 93–110. Academic Press, New YorkGoogle Scholar
  36. Kharush F (1978) The affinity of antibody: range, variability and the role of multivalence. In: Litman GW, Good RA (eds) Comprehensive immunology, vol V, immunoglobulins, pp 85–116. Plenum, New YorkGoogle Scholar
  37. Kleinsmith LJ, Stein J, Stein G (1976) Dephosphorylation of nonhistone proteins specifically alters the pattern of gene transcription in reconstituted chromatin. Proc Natl Acad Sci USA 73: 1174–1178PubMedCrossRefGoogle Scholar
  38. Koshland DE Jr (1958) Application of a theory of enzyme specificity to protein synthesis. Proc Natl Acad Sci USA 44: 98–104PubMedCrossRefGoogle Scholar
  39. Kurland CG (1978) The role of guanine nucleotides in protein biosynthesis. Biophys J 22: 373–392PubMedCrossRefGoogle Scholar
  40. Kurland CG, Rigler R, Ehrenberg M, Blomberg C (1975) Allosteric mechanism for codon-dependent tRNA selection on ribosomes. Proc Natl Acad Sci USA 72: 4248–4251PubMedCrossRefGoogle Scholar
  41. Marushije K (1976) Activation of chromatin by acetylation of histone side chains. Proc Natl Acad Sci USA 73: 3937–3941CrossRefGoogle Scholar
  42. McCulloch WS (1960) The reliability of biological systems. In: Yovits MC, Cameron S (eds) Self-organizing systems, pp 264–281. Pergamon, New YorkGoogle Scholar
  43. Menninger JR (1978) The accumulation as peptidyl-transfer RNA of isoaccepting transfer RNA families in Escherichia coli with temperature-sensitive peptidyl-transfer RNA hydrolase. J Biol Chem 253: 6808–6813PubMedGoogle Scholar
  44. Muzyczka N, Poland RL, Bessman MJ (1972) Studies on the biochemical basis of spontaneous mutation. 1. A comparison of the deoxyribonucleic acid polymerases of mutator, antimutator, and wild type strains of bacteriophage T4. J Biol Chem 247: 7116–7122PubMedGoogle Scholar
  45. Neumann J von (1956) Probabilistic logics and the synthesis of reliable organisms from unreliable components. In: Shannon CE, McCarthy J (eds) Automata studies, pp 43–98. Princeton Univ Press, PrincetonGoogle Scholar
  46. Ninio J (1974) A semi-quantitative treatment of missense and nonsense suppression in the strA and ram ribosomal mutants of Escherichia coli Evaluation of some molecular parameters of translation in vivo. J Mol Biol 84: 297–313PubMedCrossRefGoogle Scholar
  47. Ninio J (1975) Kinetic amplification of enzyme discrimination. Biochimie 57: 587–595PubMedCrossRefGoogle Scholar
  48. Ninio J (1977) Are further kinetic amplification schemes possible? Biochimie 59: 759–760PubMedCrossRefGoogle Scholar
  49. Ninio J (1979) Approches moléculaires de l’evolution. Masson, ParisGoogle Scholar
  50. Pauling L (1948) The nature of forces between large molecules of biological interest. Nature 161: 707–709PubMedCrossRefGoogle Scholar
  51. Pauling L (1958) The probability of errors in the process of synthesis of protein molecules. In: Arbeiten aus dem Gebiet der Naturstoffchemie (Festschrift Prof Dr Arthur Stoll. Zum Siebzigsten Geburtstag, 8 Januar 1957), pp 597–602. Birkhäuser, BaselGoogle Scholar
  52. Pauling L, Delbrück M (1940) The nature of the intermolecular forces operative in biological processes. Science 92: 77–79PubMedCrossRefGoogle Scholar
  53. Pfahl M (1976) Lac repressor-operator interaction. Analysis of the X86 repressor mutant. J Mol Biol 106: 857–869PubMedCrossRefGoogle Scholar
  54. Piepersberg W, Noseda V, Böck A (1979) Bacterial ribosomes with two ambiguity mutations: effects on translational fidelity, on the response to aminoglycosides and on the rate of ptotein synthesis. Mol Gen Genet 171: 23–34PubMedCrossRefGoogle Scholar
  55. Pinck M, Yot P, Chapeville F, Duranton HM (1970) Enzymatic binding of valine to the 3′ end of TYMV-RNA. Nature 226: 954–956PubMedCrossRefGoogle Scholar
  56. Richter PH (1975) A network theory of the immune system. Eur J Immunol 5: 350–354PubMedCrossRefGoogle Scholar
  57. Riggs AD, Lin S, Wells RD (1972) Lac repressor binding to synthetic DNAs of defined nucleotide sequence. Proc Natl Acad Sci USA 69: 761–764PubMedCrossRefGoogle Scholar
  58. Rosset R, Gorini L (1969) A ribosomal ambiguity mutation. J Mol Biol 39: 95–112PubMedCrossRefGoogle Scholar
  59. Silberklang M, Prochiantz A, Haenni A-L, Rajbhandary UL (1977) Studies on the sequence of the 3′-terminal region of turnip-yellow-mosaic virus RNA. Eur J Biochem 72: 465–478PubMedCrossRefGoogle Scholar
  60. Strigini P, Gorini L (1970) Ribosomal mutations affecting efficiency of amber suppression. J Mol Biol 47: 517–530PubMedCrossRefGoogle Scholar
  61. Thompson RC, Stone PJ (1977) Proofreading of the codon-anticodon interaction on ribosomes. Proc Natl Acad Sci USA 74: 198–202PubMedCrossRefGoogle Scholar
  62. Twilt JC, Overbeek GP, van Duin J (1979) Translational fidelity and specificity of ribosomes cleaved by cloacin DF13. Eur J Biochem 94: 477–484PubMedCrossRefGoogle Scholar
  63. Wang AC, Wang IY, Fudenberg HH (1977) Immunoglobulin structure and genetics. Identity between variable regions of a μ and a γ 2 chain. J Biol Chem 252: 7192–7199PubMedGoogle Scholar
  64. Watson JD, Crick FHC (1953) Molecular structure of nucleic acids. Nature 171: 738–740CrossRefGoogle Scholar
  65. Winograd S, Cowan JD (1963) Reliable computation in the presence of noise. MIT Press, Cambridge, MassGoogle Scholar
  66. Woese CR (1967) The genetic code. The molecular basis for genetic expression. Harper, New YorkGoogle Scholar
  67. Wolfenden R (1972) Analog approaches to the structure of the transition state in enzyme reactions. Acc Chem Res 5: 10–18CrossRefGoogle Scholar
  68. Yarus M (1972) Phenylalanyl-tRNA synthetase and isoleucyl-tRNAphe: a possible verification mehcanism for aminoacyl-tRNA. Proc Natl Acad Sci USA 69: 1915–1919PubMedCrossRefGoogle Scholar
  69. Yarus M, Knowlton R, Soll L (1977) Aminoacylation of the ambivalent Su 7 amber suppressor tRNA. In: Vogel HJ (ed) Nucleic acid protein recognition, pp 391–408. Academic Press, New YorkGoogle Scholar
  70. Zengel JM, Young R, Dennis PP, Nomura M (1977) Role of ribosomal protein S12 in peptide chain elongation: analysis of pleiotropic, streptomycin-resistant mutants of Escherichia coli. J Bacteriol 129: 1320–1329PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1980

Authors and Affiliations

  • J. Ninio
    • 1
  • F. Chapeville
    • 1
  1. 1.Institut de Recherche en Biologie MoleculaireUniversite de ParisParis Cedex 05France

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