Crystallization of interleukin-18 for structure-based inhibitor design

Brian Krumm; Xiangzhi Meng; Yan Xiang; Junpeng Deng

doi:10.1107/S2053230X15006871

Crystallization of interleukin-18 for structure-based inhibitor design

Brian Krumm, Xiangzhi Meng, Yan Xiang, Junpeng Deng

Microbiology, Immunology & Molecular Genetics

Research output: Contribution to journal › Article

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)
Pages (from-to)	710-717
Number of pages	8
Journal	Acta Crystallographica Section F:Structural Biology Communications
Volume	71
DOIs	https://doi.org/10.1107/S2053230X15006871
State	Published - Jun 1 2015

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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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, 710-717. https://doi.org/10.1107/S2053230X15006871

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N2 - 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.

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