Characterization of a novel and specific inhibitor for the pro-apoptotic protease Omi/HtrA2
Abbreviated Journal Title
J. Biol. Chem.
PROGRAMMED CELL-DEATH; SERINE-PROTEASE; PROTEINS; DROSOPHILA; HTRA2; GENE; XIAP; IDENTIFICATION; MITOCHONDRIA; INTERACTS; Biochemistry & Molecular Biology
Omi/HtrA2 is a mammalian serine protease with high homology to bacterial HtrA chaperones. Omi/HtrA2 is localized in mitochondria and is released to the cytoplasm in response to apoptotic stimuli. Omi/HtrA2 induces cell death in a caspase-dependent manner by interacting with the inhibitor of apoptosis protein as well as in a caspase-independent manner that relies on its protease activity. We describe the identification and characterization of a novel compound as a specific inhibitor of the proteolytic activity of Omi/HtrA2. This compound (ucf-101) was isolated in a high throughput screening of a combinatorial library using bacterially made Omi-(134-458) protease and fluorescein-casein as a generic substrate. ucf-101 showed specific activity against Omi/HtrA2 and very little activity against various other serine proteases. This compound has a natural fluorescence that was used to monitor its ability to enter mammalian cells. ucf-101, when tested in caspase-9 (-/-) null fibroblasts, was found to inhibit Omi/HtrA2-induced cell death.
Journal of Biological Chemistry
"Characterization of a novel and specific inhibitor for the pro-apoptotic protease Omi/HtrA2" (2003). Faculty Bibliography 2000s. 3679.