Crystal structure of viral serpin crmA provides insights into its mechanism of cysteine proteinase inhibition

CrmA is an unusual viral serpin that inhibits both cysteine and serine prot einases involved in the regulation of host inflammatory and apoptosis proce sses. It differs from other members of the serpin superfamily by having a r eactive center loop Chat is one residue shorter, and by its apparent inabil ity to form SDS-stable covalent complexes with cysteine proteinases. To obt ain insight into the inhibitory mechanism of crmA, we determined the crysta l structure of reactive center loop-cleaved crmA to 2.9 Angstrom resolution . The structure, which is the first of a viral serpin, suggests that crmA c an inhibit cysteine proteinases by a mechanism analogous to that used by ot her serpins against serine proteinases. However, one striking difference fr om other serpins, which may be significant for in vivo function, is an addi tional highly charged antiparallel strand for beta sheet A, whose sequence and length are unique to crmA.