Metal-chelating non-canonical amino acids in metalloprotein engineering and design

Patrick J. Almhjell, Jeremy H. Mills

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations


The ability to rationally design metalloproteins with desired functions remains a difficult challenge despite many years of effort. Recently, the potential of using genetically encoded metal-chelating non-canonical amino acids (NCAAs) to circumvent longstanding difficulties in this field has begun to be explored. In this review, we describe the development of this approach and its application to the rational design or directed evolution of NCAA-containing metalloproteins in which the bound metal ions serve in structural roles, as catalysts, or as regulators of the assembly or disassembly of protein complexes. These successes highlight the fact that amino acids not found in nature can recapitulate the functions of their naturally occurring counterparts and suggest the promise of this nascent approach for simplifying the metalloprotein design problem.

Original languageEnglish (US)
Pages (from-to)170-176
Number of pages7
JournalCurrent Opinion in Structural Biology
StatePublished - Aug 2018

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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