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Metalloprotein Design & Engineering

  1. Yi Lu

Published Online: 15 MAR 2006

DOI: 10.1002/0470862106.ia277

Encyclopedia of Inorganic Chemistry

Encyclopedia of Inorganic Chemistry

How to Cite

Lu, Y. 2006. Metalloprotein Design & Engineering. Encyclopedia of Inorganic Chemistry. .

Author Information

  1. University of Illinois at Urbana-Champaign, Urbana, IL, USA

Publication History

  1. Published Online: 15 MAR 2006


This review covers recent advances in metalloprotein design, with focus on different approaches to the design. Impressive progress has been made in designing metal-binding sites in peptides, de novo designed proteins, and native protein scaffolds. The approach can be rational or combinatorial. Under rational design, redesigning an existing metal-binding site to a new site with dramatically different structure and function complements well the design of new metal-binding sites by revealing the role of specific residues responsible for a particular structural or functional feature of the metal-binding site of interest. To create a new metal-binding site, several approaches have been used, including design based on structural homology, by inspection, using automated computer search algorithms, or combination of the above approaches. In addition, modular approach by transplanting a conserved structural unit from one protein into another has also been shown to be effective. Design through combinatorial and evolution methods has also been successful as it requires little prior knowledge of the protein structure. Finally, introducing unnatural amino acids or nonnative metal ions/prosthetic groups to expand the repertoires of metalloproteins have been demonstrated. Successful examples of each of the approaches are given; advantages and disadvantages of the approaches are discussed; the outlook for future research is also presented.


  • metalloprotein;
  • metallopeptide;
  • protein design;
  • protein engineering;
  • protein redesign;
  • de novo design;
  • rational design;
  • modular design;
  • combinatorial design;
  • unnatural amino acids;
  • motif;
  • domain;
  • phage display