Metalloenzymes are enzymes bound with metal ion at one labile coordination site. The structure of the active site is crucial for the enzymes to function. The metal ion is usually located in a pocket whose shape fits the substrate.

The thioether-bonded tyrosine-cysteine cofactor is ubiquitous for diverse metalloenzymes. Because of the fascinating chemistry and potential industrial applications of these enzymes, the functional significance of the essential Tyr-Cys cofactor has been intensively investigated by synthetic chemists, physical chemists, enzymologists, and structure biologists, and tremendous progress has been made in this area.

Professor WANG Jiangyun at the Institute of Biophysics, Chinese Academy of Sciecnes recently published an article onAngewandte Chemie International Edition, titled “Probing the Function of the Tyr-Cys Cross-Link in Metalloenzymes by the Genetic Incorporation of 3-Methylthiotyrosine”. He reports that the genetic incorporation of a new unnatural amino acid (UAA) 2-amino-3-(4-hydroxy -3-(methylthio)phenyl)propanoic acid, which mimics the Tyr–Cys cofactor, into a functional model of TvNiR in sperm whale myoglobin (Mb).

This research gives new insights into the Tyr-Cys cofactor function. And the new method for the genetic incorporation of MtTyr should allow for the rapidly evolution of metalloenzymes with specific activity towards various monosaccharides, by using well characterized protein maquettes as a copper ligand and by applying rational and computational design methods.

Professor WANG’s work was supported by grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China and the Chinese Academy of Sciences.

Fig.  A) Structural alignment of Wolinella succinogenes cytochrome c nitrite reductase and TvNiR.  B) Structural model of MtTyrMb