Proteins can catalyze a wide range of chemical reactions. Yet the main differences between polypeptides are in the side chains of naturally occurring amino acids, which account for only a small fraction of the potential chemical functionality. Instead the diversity of function is made possible partly because proteins can incorporate cofactors – such as small organic molecules, single metal atoms or clusters containing metal and non-metal atoms – in their active sites.
About half of all enzymes require the presence of a metal atom to function. These ‘metalloproteins’ have fascinated chemists and biochemists, especially since the 1950s, when the first X-ray crystal structure of the protein, the sperm whale myoglobin, indicated the presence of an iron atom.
Much is understood about how metal groups are assembled, how metal ions or clusters are introduced into target proteins, and which metal ions are commonly found in metal cations. Furthermore, we are much closer to understanding the mechanisms by which metalenzymes catalyze a range of complex chemical reactions. But, despite more than half a century of research by chemists, biochemists and cell biologists, many discoveries remain to be made.
Articles from this insight shed light on some of the most exciting current research on metalloproteins, including how enzymes containing complex metal groups metabolize small gaseous molecules, how proteins containing iron-sulfur groups are assembled, and How small organic molecules containing a metal ion catalyze the halogenation of a metalloenzyme.
We are pleased to acknowledge AstraZeneca’s financial support in building this insight. As always, Nature takes full responsibility for all editorial content and peer review.