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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Krumm
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078, USA.
authors.forename: Junpeng
authors.initials: J
authors.lastname: Deng
mesh_terms: D020816:Amino Acid Motifs; D003460:Crystallization; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry; D020382:Interleukin-18 / Q000737:chemistry* / Q000235:genetics; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009994:Osmolar Concentration; D011485:Protein Binding; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: C000589760:IL18 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D008024:Ligands; D011993:Recombinant Fusion Proteins; C118370:interleukin-18 binding protein
keywords: cytokines; immune defense; interleukin-18; surface-entropy reduction