Chimeric protein engineering

Jianwen A. Feng, Lee A. Tessler, Garland R. Marshall

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Protein stability can be enhanced by the incorporation of non-natural amino acids and semi-rigid peptidomimetics to lower the entropic penalty upon protein folding through preorganization. An example is the incorporation of aminoisobutyric acid (Aib, α-methylalanine) into proteins to restrict the Φ and Ψ backbone angles adjacent to Aib to those associated with helix formation. Reverse-turn analogs were introduced into the sequences of HIV protease and ribonuclease A that enhanced their stability and retained their native enzymatic activity. In this work, a chimeric protein, design_4, was engineered, in silico, by replacing the C-terminal helix of full sequence design protein (FSD-1) with a semi-rigid helix mimetic. Residues 1-16 of FSD-1 was ligated in silico with the N-terminus of a phenylbipyridyl-based helix mimetic to form design_4. The designed chimeric protein was stable and maintained the designed fold in a 100-nanosecond molecular dynamics simulation at 280 K. Its β-hairpin adopted conformations that formed three additional hydrogen bonds. Compared to FSD-1, design_4 contained fewer peptide bonds and internal degrees of freedom; it should, therefore, be more resistant to proteolytic degradation and denaturation.

Original languageEnglish
Pages (from-to)151-160
Number of pages10
JournalInternational Journal of Peptide Research and Therapeutics
Volume13
Issue number1-2
DOIs
StatePublished - Jun 1 2007

Keywords

  • Chimeric protein
  • Helix mimetic
  • Peptidomimetic
  • Protein engineering

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