Emulating the properties of metalloproteins remains a challenge. Given that such materials represent an important cohort of all proteins, researchers at the University of Michigan, USA, and the University of Birmingham, UK, believe it is a worthwhile pursuit.

The team has now produced the first de novo designed hydrolytic metalloenzyme and used kinetics and X-ray structural analysis to reveal the design features that give it activity. It contained two different metal ions — a Zn(II) ion, for catalytic activity, and a Hg(II) ion, which provides structural stability. It catalysed p-nitrophenyl acetate hydrolysis with an efficiency only ~100-fold less than that of human carbonic anhydrase. It was approximately 550-fold better than comparable synthetic complexes.

The work could point to the development of other active and potent enzyme mimics that bear at least one metal ion.

• Hydrolytic catalysis and structural stabilization in a designed metalloprotein
  M. L. Zastrow, A. F. A. Peacock, J. A. Stuckey, V. L. Pecoraro,
  Nature Chem. 2011.
  DOI: 10.1038/nchem.1201