Journal of Molecular Biology
Volume 217, Issue 4, 20 February 1991, Pages 721-729
Journal home page for Journal of Molecular Biology

Article
Suggestions for “safe” residue substitutions in site-directed mutagenesis

https://doi.org/10.1016/0022-2836(91)90528-EGet rights and content

Abstract

The conserved topological structure observed in various molecular families such as globins or cytochromes c allows structural equivalencing of residues in every homologous structure and defines in a coherent way a global alignment in each sequence family. A search was performed for equivalent residue pairs in various topological families that were buried in protein cores or exposed at the protein surface and that had mutated but maintained similar unmutated environments. Amino acid residues with atoms in contact with the mutated residue pairs defined the environment. Matrices of preferred amino acid exchanges were then constructed and preferred or avoided amino acid substitutions deduced. Given the conserved atomic neighborhoods, such natural in vivo substitutions are subject to similar constraints as point mutations performed in site-directed mutagenesis experiments. The exchange matrices should provide guidelines for “safe” amino acid substitutions least likely to disturb the protein structure, either locally or in its overall folding pathway, and most likely to allow probing of the structural and functional significance of the substituted site.

References (81)

  • P. Argos

    Methods Enzymol

    (1990)
  • Y.S. Babu et al.

    J. Mol. Biol

    (1988)
  • D. Bashford et al.

    J. Mol. Biol

    (1987)
  • F.C. Bernstein et al.

    J. Mol. Biol

    (1977)
  • W. Bode et al.

    J. Mol. Biol

    (1983)
  • D. Bordo et al.

    J. Mol. Biol

    (1990)
  • G. Fermi et al.

    J. Mol. Biol

    (1984)
  • J.A. Frier et al.

    J. Mol. Biol

    (1977)
  • M. Fujinaga et al.

    J. Mol. Biol

    (1987)
  • M. Fujinaga et al.

    J. Mol. Biol

    (1985)
  • W. Furey et al.

    J. Mol Biol

    (1983)
  • W.A. Hendrickson et al.

    J. Mol. Biol

    (1973)
  • P. Hopper et al.

    J. Mol. Biol

    (1984)
  • M.N.G. James et al.

    J. Mol. Biol

    (1983)
  • T.A. Jones et al.

    J. Mol. Biol

    (1984)
  • A.M. Lesk et al.

    J. Mol. Biol

    (1980)
  • A.M. Lesk et al.

    J. Mol. Biol

    (1982)
  • M. Marquart et al.

    J. Mol. Biol

    (1980)
  • Y. Matsuura et al.

    J. Mol. Biol

    (1982)
  • J. Moult et al.

    J. Mol. Biol

    (1985)
  • H. Ochi et al.

    J. Mol. Biol

    (1983)
  • S.E.V. Phillips

    J. Mol. Biol

    (1980)
  • R.J. Read et al.

    J. Mol. Biol

    (1988)
  • M.G. Rossmann et al.

    J. Mol. Biol

    (1976)
  • M.G. Rossmann et al.

    J. Mol. Biol

    (1977)
  • F.R. Salemme et al.

    J. Biol. Chem

    (1973)
  • A. Sali et al.

    Trends Biochem. Sci

    (1990)
  • K.A. Satyshur et al.

    J. Biol. Chem

    (1988)
  • F.A. Saul et al.

    J. Biol. Chem

    (1978)
  • H. Scouloudi et al.

    J. Mol. Biol

    (1978)
  • W. Steigemann et al.

    J. Mol. Biol

    (1979)
  • K. Suguna et al.

    J. Mol. Biol

    (1987)
  • D.M. Szebenyi et al.

    J. Biol. Chem

    (1986)
  • R. Timkovich et al.

    J. Biol. Chem

    (1976)
  • H. Tsukada et al.

    J. Mol. Biol

    (1985)
  • R.A. Alden et al.

    Biochem. Biophys. Res. Commun

    (1971)
  • L.M. Amzel et al.

    Annu. Rev. Biochem

    (1979)
  • P. Argos et al.

    Biochemistry

    (1979)
  • E. Arnold et al.

    Acta Crystallogr. sect. A

    (1988)
  • W. Bode et al.

    Eur. J. Biochem

    (1987)
  • Cited by (357)

    • Properties of proteins in food systems: An introduction

      2018, Proteins in Food Processing: Second Edition
    • Properties of proteins in food systems: An introduction

      2017, Proteins in Food Processing, Second Edition
    • Structure determination of the nucleosome core particle by selenium SAD phasing

      2019, Acta Crystallographica Section D: Structural Biology
    • ExplainableFold: Understanding AlphaFold Prediction with Explainable AI

      2023, Proceedings of the ACM SIGKDD International Conference on Knowledge Discovery and Data Mining
    View all citing articles on Scopus
    View full text