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Bioenergetics pp 125-145 | Cite as

How Well is Cytochrome c Engineered?

  • Emanuel Margoliash
  • Abel Schejter
  • Thomas I. Koshy
  • Thomas L. Luntz
  • Eric A. E. Garber

Summary

For a protein as old as cytochrome c, which shows exquisite adaptation to its particular environment in the species carrying it, and which has been extensively studied, the properties of site-directed mutants should be readily predictable and fall within our understanding of how the evolutionary process has operated on the protein. Among the relatively few mutants at evolutionarily constant residues studied so far, some yield cytochromes c of apparently normal functionality and dramatically greater stability than the wild-type protein. This poses the question of how close to structural perfection have the present day cytochromes c evolved?

Examples are discussed of such stabilization mutants at tyrosine 67, asparagine 52 and threonine 78, all three residues being hydrogen bonded to a molecule of water held in the interior of the protein. In contrast, mutants at the invariant proline 30 show the expected deterioration in function. To explain this situation, it is suggested that the mutations of this series which impart improved stability, are nevertheless potentially deleterious in that they may allow mutations at other sites, which would otherwise be of minor consequence, to result in a grossly disturbed protein. Such an evolutionarily important phenomenon may be termed second site deficiency. The significant energetic cost of maintaining the internal water molecule structure of the native protein, which appears to be the function held in common by residues 67, 52 and 78, may be used to preclude such a drastic eventuality, thereby keeping open a variety of evolutionary pathways to the protein that would otherwise be forbidden.

Keywords

HPLC Urea Glycine Respiration Serine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Emanuel Margoliash
    • 1
  • Abel Schejter
    • 2
  • Thomas I. Koshy
    • 1
  • Thomas L. Luntz
    • 1
  • Eric A. E. Garber
    • 1
  1. 1.Department of Biochemistry, Molecular Biology and Cell BiologyNorthwestern UniversityEvanstonUSA
  2. 2.Sackler Institute of Molecular Biology, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

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