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 › peer-review

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

Biophysics
Structural Biology
Biochemistry
Genetics
Condensed Matter Physics

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title = "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.",

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author = "Brian Krumm and Xiangzhi Meng and Yan Xiang and Junpeng Deng",

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T1 - Crystallization of interleukin-18 for structure-based inhibitor design

AU - Krumm, Brian

AU - Meng, Xiangzhi

AU - Xiang, Yan

AU - Deng, Junpeng

PY - 2015/6/1

Y1 - 2015/6/1

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.

AB - 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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KW - immune defense

KW - interleukin-18

KW - surface-entropy reduction

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Crystallization of interleukin-18 for structure-based inhibitor design

Abstract

Keywords

ASJC Scopus subject areas

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