Structure and mechanism of interleukin-1 beta converting enzyme.
Interleukin-1 beta converting enzyme (ICE) processes an inactive precursor to the proinflammatory cytokine, interleukin-1 beta, and may regulate programmed cell death in neuronal cells. The high-resolution structure of human ICE in complex with an inhibitor has been determined by X-ray diffraction. The structure confirms the relationship between human ICE and cell-death proteins in other organisms. The active site spans both the 10 and 20K subunits, which associate to form a tetramer, suggesting a mechanism for ICE autoactivation.
Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139.
K P
KP
Wilson
J A
JA
Black
J A
JA
Thomson
E E
EE
Kim
J P
JP
Griffith
M A
MA
Navia
M A
MA
Murcko
S P
SP
Chambers
R A
RA
Aldape
S A
SA
Raybuck
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D020170:Caspase 1; D002384:Catalysis; D016923:Cell Death; D002460:Cell Line; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007700:Kinetics; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins
D007375:Interleukin-1; D011994:Recombinant Proteins; D020170:Caspase 1; D008666:Metalloendopeptidases