Harnessing protein symmetry for enzyme design

Bigna Wörsdörfer, Lisa M. Henning, Richard Obexer, Donald Hilvert*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

15 Citations (Scopus)

Abstract

Cyclic protein oligomers are common in Nature. Here we show that the central pore of the pentameric ring-forming protein lumazine synthase from Saccharomyces cerevisiae (ScLS) can be rationally engineered to catalyze a retro-aldol reaction. The C 5-symmetry of the complex was exploited to equip the protein tunnel with a ring of five closely spaced lysines adjacent to an apolar site for substrate binding. The resulting system utilizes amine catalysis to promote the cleavage of (±)-methodol to 6-methoxy-2- naphthaldehyde and acetone with a >10 3-fold rate acceleration. The ease of organizing convergent functional groups within a protein pore may make the tunnels of many symmetric ring-shaped proteins useful starting points for creating designer enzymes.

Original languageEnglish
Pages (from-to)982-985
Number of pages4
JournalACS Catalysis
Volume2
Issue number6
DOIs
Publication statusPublished - 1 Jun 2012

Keywords

  • aldol reaction
  • amine catalysis
  • convergent design
  • enzyme models

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