Mechanisms of protein evolution and their application to protein engineering

Margaret E. Glasner, John Alan Gerlt, Patricia C. Babbitt

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Protein engineering holds great promise for the development of new biosensors, diagnostics, therapeutics, and agents for bioremediation. Despite some remarkable successes in experimental and computational protein design, engineered proteins rarely achieve the efficiency or specificity of natural enzymes. Current protein design methods utilize evolutionary concepts, including mutation, recombination, and selection, but the inability to fully recapitulate the success of natural evolution suggests that some evolutionary principles have not been fully exploited. One aspect of protein engineering that has received little attention is how to select the most promising proteins to serve as templates, or scaffolds, for engineering. Two evolutionary concepts that could provide a rational basis for template selection are the conservation of catalytic mechanisms and functional promiscuity. Knowledge of the catalytic motifs responsible for conserved aspects of catalysis in mechanistically diverse superfamilies could be used to identify promising templates for protein engineering. Second, protein evolution often proceeds through promiscuous intermediates, suggesting that templates which are naturally promiscuous for a target reaction could enhance protein engineering strategies. This review explores these ideas and alternative hypotheses concerning protein evolution and engineering. Future research will determine if application of these principles will lead to a protein engineering methodology governed by predictable rules for designing efficient, novel catalysts.

Original languageEnglish (US)
Title of host publicationProtein Evolution
EditorsEric Toone
Pages193-239
Number of pages47
StatePublished - Jan 11 2007

Publication series

NameAdvances in Enzymology and Related Areas of Molecular Biology
Volume75
ISSN (Print)0065-258X

Fingerprint

Protein Engineering
Proteins
Environmental Biodegradation
Biosensing Techniques
Catalysis
Genetic Recombination
Bioremediation
Mutation
Biosensors
Enzymes
Scaffolds
Conservation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Glasner, M. E., Gerlt, J. A., & Babbitt, P. C. (2007). Mechanisms of protein evolution and their application to protein engineering. In E. Toone (Ed.), Protein Evolution (pp. 193-239). (Advances in Enzymology and Related Areas of Molecular Biology; Vol. 75).

Mechanisms of protein evolution and their application to protein engineering. / Glasner, Margaret E.; Gerlt, John Alan; Babbitt, Patricia C.

Protein Evolution. ed. / Eric Toone. 2007. p. 193-239 (Advances in Enzymology and Related Areas of Molecular Biology; Vol. 75).

Research output: Chapter in Book/Report/Conference proceedingChapter

Glasner, ME, Gerlt, JA & Babbitt, PC 2007, Mechanisms of protein evolution and their application to protein engineering. in E Toone (ed.), Protein Evolution. Advances in Enzymology and Related Areas of Molecular Biology, vol. 75, pp. 193-239.
Glasner ME, Gerlt JA, Babbitt PC. Mechanisms of protein evolution and their application to protein engineering. In Toone E, editor, Protein Evolution. 2007. p. 193-239. (Advances in Enzymology and Related Areas of Molecular Biology).
Glasner, Margaret E. ; Gerlt, John Alan ; Babbitt, Patricia C. / Mechanisms of protein evolution and their application to protein engineering. Protein Evolution. editor / Eric Toone. 2007. pp. 193-239 (Advances in Enzymology and Related Areas of Molecular Biology).
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