-homoserine product bound at the dizinc metal center. The zinc ions are shown as cyan spheres. All ligand molecules are shown in ball-and-stick form. Carbon, oxygen, and nitrogen atoms are colored white, red, and blue, respectively. -->
A dinuclear zinc binding site is conserved in all known lactonases and essential for enzyme activity and protein folding.
Zn1 is tetracoordinated by His104, His106, His169, and the bridging hydroxide ion. Zn2 has five ligands, including Asp191, His235, His109, Asp108, and the bridging hydroxide ion. The metal ions assist in polarizing the lactone bond, increasing the electrophilicity of the lactone ring’s carbonyl carbon. Isotopic labeling studies indicated that the ring opening occurs via an addition elimination reaction with water addition shown below.