What Are Caspase Inhibitors?

Caspases are a group of structurally related cysteine proteases found in cytosol in recent years. An important common feature of them is that the active sites contain cysteine and specifically cut off aspartate Peptide bond after acid residue. The term Caspase is derived from the acronym Cysteine aspartic acid specific protease, which reflects this feature, and this high specificity is rare in proteases.

Caspase family

Because of this specificity,

At least 11 caspases have been identified:

Among these caspases, caspase 1 and caspase 11 and possibly caspase 4 are not considered to be directly involved in the transduction of apoptosis signals, and they are mainly involved in the activation of interleukin precursors; while caspase 2, caspase 8, caspase 9 and caspase 10 are involved Initiation of apoptosis; caspase 3, caspase 6 and caspase 7 are involved in the execution of apoptosis, of which caspase 3 and 7 have similar substrate and inhibitor specificity, and they degrade PARP, DFF-45 (DNA fragmentation factor-45), which leads to inhibition of DNA repair and initiates DNA degradation. The substrates of caspase-6 are lamin A and keratin 18. Their degradation leads to the disintegration of nuclear fibrous layer and cytoskeleton.

Caspase synthesized in the cell exists in an inactive zymogen state, and it can perform its function after being activated.

In general protease activation, only the N-terminal peptide is excised, and caspase activation requires cleavage at the aspartic acid site at the junction of the two subunits. Heterodimer, which is an active enzyme. Generally, the N-terminal peptide is also removed during activation, but it has no effect on the activity of whether or not caspase 7 removes the N-terminal peptide. It is currently believed that there is an upstream and downstream relationship between the initiators (caspase 2, 8, 9 and 10) and the performers (caspase 3, 6 and 7), that is, the initiator activates the performer.

The activation of apoptotic initiators (caspase 2, and 10) is a homosexual activation (Homo activation). caspase 8 and 10 contain tandem repeat "death effector domain" (DED), while caspase 2 and 9 contain different but similar caspase recruitment domain CARD, these two domains It is necessary to recruit caspase 2, 8 and 10.

caspase-8 stops apoptosis, is able to cleave RIP1 and RIP3, effectively terminating necrosis.