Crystallization of interleukin-18 for structure-based inhibitor design

Brian Krumm, Xiangzhi Meng, Yan Xiang, Junpeng Deng

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)710-717
Number of pages8
JournalActa Crystallographica Section F:Structural Biology Communications
Volume71
DOIs
Publication statusPublished - Jun 1 2015

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Keywords

  • cytokines
  • immune defense
  • interleukin-18
  • surface-entropy reduction

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics
  • Structural Biology
  • Condensed Matter Physics

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