Sumner's legacy: a century of urease crystals and recent structural advances

In 1926, James B. Sumner crystallized jack bean urease-the first enzyme to be obtained in crystalline form-thus demonstrating that enzymes are proteinaceous. To honor the 100-year anniversary of that momentous event, this review highlights critical findings leading up to Sumner's efforts, explains the significance of his results, and describes subsequent experimental findings related to urease. For example, nearly five decades after crystals became available Burt Zerner and colleagues identified urease as the first known nickel-containing enzyme. The surprising discovery of nickel in urease raised questions about the structure of the metal-containing active site, the enzyme mechanism, and pathway by which the catalytic center is synthesized - each of which is addressed here. Finally, I reflect on remaining open questions related to this remarkable enzyme and potential experimental directions that could be employed to provide corresponding insights.