PMID- 26057800
OWN - NLM
STAT- MEDLINE
DCOM- 20160307
LR  - 20231111
IS  - 2053-230X (Electronic)
IS  - 2053-230X (Linking)
VI  - 71
IP  - Pt 6
DP  - 2015 Jun
TI  - Crystallization of interleukin-18 for structure-based inhibitor design.
PG  - 710-7
LID - 10.1107/S2053230X15006871 [doi]
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.
FAU - Krumm, Brian
AU  - Krumm B
AD  - Department of Biochemistry and Molecular Biology, Oklahoma State University, 
      Stillwater, OK 74078, USA.
FAU - Meng, Xiangzhi
AU  - Meng X
AD  - Department of Microbiology and Immunology, University of Texas Health Science 
      Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
FAU - Xiang, Yan
AU  - Xiang Y
AD  - Department of Microbiology and Immunology, University of Texas Health Science 
      Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
FAU - Deng, Junpeng
AU  - Deng J
AD  - Department of Biochemistry and Molecular Biology, Oklahoma State University, 
      Stillwater, OK 74078, USA.
LA  - eng
SI  - PDB/4XFS
SI  - PDB/4XFT
SI  - PDB/4XFU
GR  - R01 AI079217/AI/NIAID NIH HHS/United States
GR  - R21 AI113539/AI/NIAID NIH HHS/United States
GR  - AI079217/AI/NIAID NIH HHS/United States
GR  - AI113539/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20150520
PL  - United States
TA  - Acta Crystallogr F Struct Biol Commun
JT  - Acta crystallographica. Section F, Structural biology communications
JID - 101620319
RN  - 0 (IL18 protein, human)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-18)
RN  - 0 (Ligands)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (interleukin-18 binding protein)
SB  - IM
MH  - Amino Acid Motifs
MH  - Crystallization
MH  - Crystallography, X-Ray
MH  - Escherichia coli/genetics/metabolism
MH  - Gene Expression
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/chemistry
MH  - Interleukin-18/*chemistry/genetics
MH  - Ligands
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Osmolar Concentration
MH  - Protein Binding
MH  - *Protein Engineering
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - Recombinant Fusion Proteins/*chemistry/genetics
MH  - Surface Properties
MH  - Thermodynamics
PMC - PMC4461335
OTO - NOTNLM
OT  - cytokines
OT  - immune defense
OT  - interleukin-18
OT  - surface-entropy reduction
EDAT- 2015/06/10 06:00
MHDA- 2016/03/08 06:00
PMCR- 2016/06/01
CRDT- 2015/06/10 06:00
PHST- 2015/01/16 00:00 [received]
PHST- 2015/04/06 00:00 [accepted]
PHST- 2015/06/10 06:00 [entrez]
PHST- 2015/06/10 06:00 [pubmed]
PHST- 2016/03/08 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - S2053230X15006871 [pii]
AID - sw5081 [pii]
AID - 10.1107/S2053230X15006871 [doi]
PST - ppublish
SO  - Acta Crystallogr F Struct Biol Commun. 2015 Jun;71(Pt 6):710-7. doi: 
      10.1107/S2053230X15006871. Epub 2015 May 20.