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Crystallization of interleukin‐18 for structure‐based inhibitor design
Author(s) -
Krumm Brian,
Meng Xiangzhi,
Xiang Yan,
Deng Junpeng
Publication year - 2015
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x15006871
Subject(s) - rational design , interleukin 1 receptor antagonist , drug design , immune system , antagonist , in vivo , cytokine , crystallization , receptor , microbiology and biotechnology , computational biology , receptor antagonist , biology , immunology , chemistry , bioinformatics , biochemistry , genetics , organic chemistry
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.