Structure and zymogen activation of caspases.
Apoptosis is primarily executed by active caspases, which are derived from the inactive zymogens. Structural and biochemical studies of caspases-1, -3, -7, -8 and -9 have greatly enhanced our understanding of the structure, function, and specificity of the active form of these enzymes. Only recently, the structures of procaspase-7 and biochemical studies of procaspase-9 and -8 have provided insight into the process of procaspase activation. The mechanism of zymogen activation requires limited proteolysis as for many other proteases. In addition, self-activation through oligomerization has been demonstrated for the initiator caspases-8, -9 and -10. These studies provide a structural mechanism for caspase activation, substrate/inhibitor binding, and contribute to the understanding of the biological role of caspases in the processes of apoptosis.
Donepudi
Mrudula
M
Institute of Biochemistry, University of Zürich, Winterthurerstr 190, 8057 Zurich, Switzerland.
Grütter
Markus G
MG
D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D013379:Substrate Specificity
D004792:Enzyme Precursors; D020169:Caspases