Crystallization of interleukin-18 for structure-based inhibitor design
Abstract
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.
Citation
Krumm, B., Meng, X., Xiang, Y., & Deng, J. (2015). Crystallization of interleukin-18 for structure-based inhibitor design. Acta Crystallographica Section F - Structural Biology Communications, 71(6), 710-717. https://doi.org/10.1107/S2053230X15006871