Interleukin-18 (IL-18) is a pleiotropic pro-inflammatory cytokine belonging to
the IL-1 superfamily. IL-18 plays an important role in host innate and acquired
immune defense, with its activity being modulated in vivo by its naturally
occurring antagonist IL-18 binding protein (IL-18BP). Recent crystal structures
of human IL-18 (hIL-18) in complex with its antagonist or cognate receptor(s)
have revealed a conserved binding interface on hIL-18 representing a promising
drug target. An important step in this process is obtaining crystals of apo
hIL-18 or hIL-18 in complex with small-molecule inhibitors, preferably under low
ionic strength conditions. In this study, surface-entropy reduction (SER) and
rational protein design were employed to facilitate the crystallization of
hIL-18. The results provide an excellent platform for structure-based drug
design.
