Front Cover: Kemp Eliminases of the AlleyCat Family Possess High Substrate Promiscuity (ChemCatChem 5/2019)

The Front Cover picture shows that AlleyCat2, a member of the AlleyCat family of allosterically regulated Kemp eliminases, is capable of binding leflunomide, an immunosuppressant drug, and converting it into teriflunomide, its active form, with remarkable efficiency. In their Communication, E. A. Caselle, J. H. Yoon et al. show that small libraries of designed catalysts provide fertile ground for discovering new reactivities. AlleyCat2 relies on a high pKa of the active base and proper positioning of the substrate in the hydrophobic cleft of the enzyme to promote catalysis. This work also demonstrates that using pH rate profiles to determine the pKa of the active residue can be quite misleading and NMR studies that can probe specific atoms directly provide invaluable mechanistic information. More information can be found in the Communication by E. A. Caselle, J. H. Yoon et al. on page 1425 in Issue 5, 2019 (DOI: 10.1002/cctc.201801994).