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crmA, or cytokine response modifier A, is a cowpox serpin that inhibits caspases 1, 6 and 8, forming complexes with these caspases that renders them unable to perform their apoptotic functions. Cowpox is an orthopox virus that increases their chances of survival and infection by inhibition of specific caspases and preventing inflammatory responses and apoptosis.
Serpins generally inhibit serine proteases by a suicide substrate inhibition mechanism, in which the serpin undergoes a drastic change in structure to form an acyl enzyme intermediate. A reactive center loop of the protease is bound to the central beta loop of the serpin, trapping the protease in a state where it is no longer able to perform its catalytic functions. Studies have shown crmA uses a method analogous to serpin inhibition of serine proteases to inhibit cysteine protease caspases.
The Inhibitors of apoptosis proteins are a family of functionally and structurally related proteins that serve as endogenous inhibitors of programmed cell death. A common feature of all IAPs is the presence of a BIR in one to three copies. The human IAP family consists of 8 members, and IAP homologs have been identified in numerous organisms.
The first members of the IAPs identified were from the baculovirus IAPs, Cp-IAP and Op-IAP, which bind to and inhibit caspases as a mechanism that contributes to its efficient infection and replication cycle in the host. Later, five more human IAPs were discovered which included XIAP, cIAP1 , C-IAP2, NAIP, Livin and Survivin.