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.
Original language | English (US) |
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Pages (from-to) | 710-717 |
Number of pages | 8 |
Journal | Acta Crystallographica Section F:Structural Biology Communications |
Volume | 71 |
DOIs | |
State | Published - Jun 1 2015 |
Keywords
- cytokines
- immune defense
- interleukin-18
- surface-entropy reduction
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Genetics
- Condensed Matter Physics