title: Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer.
abstract: Interleukin-1 beta-converting enzyme (ICE) proteolytically cleaves pro-IL-1 beta to its mature, active form. The crystal structure at 2.5 A resolution of a recombinant human ICE-tetrapeptide chloromethylketone complex reveals that the holoenzyme is a homodimer of catalytic domains, each of which contains a p20 and a p10 subunit. The spatial separation of the C-terminus of p20 and the N-terminus of p10 in each domain suggests two alternative pathways of assembly and activation in vivo. ICE is homologous to the C. elegans cell death gene product, CED-3, and these may represent a novel class of cytoplasmic cysteine proteases that are important in programmed cell death (apoptosis). Conservation among members of the ICE/CED-3 family of the amino acids that form the active site region of ICE supports the hypothesis that they share functional similarities.
authors.affiliation: BASF Aktiengesellschaft, Main Laboratory, Ludwigshafen, Federal Republic of Germany.
authors.forename: N P
authors.initials: NP
authors.lastname: Walker
authors.forename: R V
authors.initials: RV
authors.lastname: Talanian
authors.forename: K D
authors.initials: KD
authors.lastname: Brady
authors.forename: L C
authors.initials: LC
authors.lastname: Dang
authors.forename: N J
authors.initials: NJ
authors.lastname: Bump
authors.forename: C R
authors.initials: CR
authors.lastname: Ferenz
authors.forename: S
authors.initials: S
authors.lastname: Franklin
authors.forename: T
authors.initials: T
authors.lastname: Ghayur
authors.forename: M C
authors.initials: MC
authors.lastname: Hackett
authors.forename: L D
authors.initials: LD
authors.lastname: Hammill
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D000595:Amino Acid Sequence; D017209:Apoptosis; D003460:Crystallization; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D011994:Recombinant Proteins; D015843:Serpins; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor