Abstract
Interleukin-1 beta (IL-1 beta)-converting enzyme cleaves the IL-1 beta precursor to mature IL-1 beta, an important mediator of inflammation. The identification of the enzyme as a unique cysteine protease and the design of potent peptide aldehyde inhibitors are described. Purification and cloning of the complementary DNA indicates that IL-1 beta-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis. Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1 beta, indicating that it is a potential therapeutic target.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Binding, Competitive / drug effects
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Caspase 1
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Chromatography, Affinity
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Chromatography, DEAE-Cellulose
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Chromatography, High Pressure Liquid
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Chromosome Mapping
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Cloning, Molecular
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Diazomethane / analogs & derivatives
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Diazomethane / pharmacology
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Electrophoresis, Polyacrylamide Gel
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Humans
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Interleukin-1 / metabolism*
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Metalloendopeptidases / chemistry
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Metalloendopeptidases / genetics
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Metalloendopeptidases / isolation & purification
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Metalloendopeptidases / physiology*
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Molecular Sequence Data
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Monocytes / enzymology*
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Open Reading Frames
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Protein Processing, Post-Translational
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Sequence Homology, Nucleic Acid
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Substrate Specificity
Substances
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Interleukin-1
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diazomethyl ketones
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Diazomethane
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Caspase 1
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Metalloendopeptidases