Modified interleukin-1beta converting enzyme with increased stability

A modified interleukin-1β converting enzyme (ICE) comprising an amino acid sequence wherein an amino acid corresponding to aspartic acid at position 381 of unmodified ICE (SEQ ID NO:

• 2) is replaced with glutamic acid.

A modified interleukin-1β converting enzyme (ICE) comprising an amino acid sequence wherein an amino acid corresponding to aspartic acid at position 381 of unmodified ICE (SEQ ID NO:

• 2) is replaced with an amino acid selected from the group consisting of serine, threonine, asparagine and glutamine.

A nucleic acid molecule encoding a modified p10 subunit of interleukin-1β converting enzyme (ICE), the modified p10 subunit comprising an amino acid sequence wherein an amino acid corresponding to aspartic acid at position 381 of unmodified ICE (SEQ ID NO:

• 2) is replaced with a mutant amino acid structure, the mutant amino acid structure being capable of forming a salt bridge with an amino acid corresponding to arginine at position 383 of unmodified ICE, such that the modified p10 subunit associates with a p20 subunit to form a modified ICE which retains proteolytic activity and exhibits increased stability compared to unmodified ICE.

A nucleic acid molecule encoding a modified p10 subunit of interleukin-1β converting enzyme (ICE), the modified p10 subunit comprising an amino acid sequence wherein an amino acid corresponding to aspartic acid at position 381 of unmodified ICE (SEQ ID NO:

• 2) is replaced with glutamic acid.

A nucleic acid molecule encoding a modified p10 subunit of interleukin-1β converting enzyme (ICE), the modified p10 subunit comprising an amino acid sequence wherein an amino acid corresponding to aspartic acid at position 381 of unmodified ICE (SEQ ID NO:

• 2) is replaced with an amino acid selected from the group consisting of serine, threonine, asparagine and glutamine.

A method for cleaving an interleukin-1β converting enzyme (ICE) substrate, comprising contacting the substrate with a modified ICE such that the ICE substrate is cleaved, wherein the modified ICE comprises an amino acid sequence having an amino acid corresponding to aspartic acid at position 381 of unmodified ICE (SEQ ID NO:

• 2) replaced with a mutant amino acid structure, the mutant amino acid structure being capable of forming a salt bridge with an amino acid corresponding to arginine at position 383 of unmodified ICE.