IL-1-converting enzyme requires aspartic acid residues for processing of the IL-1 beta precursor at two distinct sites and does not cleave 31-kDa IL-1 alpha.

摘要: IL-1 converting enzyme (ICE) specifically cleaves the human beta precursor at two sequence-related sites: Asp27-Gly28 (site 1) and Asp116-Ala117 2). Cleavage results in generation of mature, biologically active beta. ICE is unusual that preferred cleavage Asp-X bonds (where X a small hydrophobic residue), has not been described for any other eukaryotic protease. To further examine substrate specificity ICE, proteins contain linkages including transferrin, actin, complement factor 9, murine precursor, alpha precursors, were assayed by 500-fold purified ICE. The precursors only cleaved demonstrating an convertase. Analysis mutants containing amino acid substitutions or deletions within each processing site demonstrated omission replacement Asp 1 2 prevented quantitatively assess requirements peptide-based assay was established using 14-mer spanning 2. between [P1] Ala [P1']2 demonstrated. Replacement with Ala, Glu, Asn resulted greater than 100-fold reduction activity. rank order position P1' Gly much Leu Lys Glu. Substitutions P2'-P4' P6' had relatively little effect on These show highly specific convertase absolute P1 P1'.