Premium
Crystal structure of viral serpin crmA provides insights into its mechanism of cysteine proteinase inhibition
Author(s) -
Simonovic Miljan,
Gettins PETER G. W.,
Volz Karl
Publication year - 2000
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.9.8.1423
Subject(s) - serpin , cysteine , serine , serine proteinase inhibitors , antiparallel (mathematics) , cysteine protease , proteases , capsid , peptide sequence , chemistry , protein structure , serine protease , biology , biochemistry , microbiology and biotechnology , protease , enzyme , physics , quantum mechanics , magnetic field , gene
CrmA is an unusual viral serpin that inhibits both cysteine and serine proteinases involved in the regulation of host inflammatory and apoptosis processes. It differs from other members of the serpin superfamily by having a reactive center loop that is one residue shorter, and by its apparent inability to form SDS‐stable covalent complexes with cysteine proteinases. To obtain insight into the inhibitory mechanism of crmA, we determined the crystal structure of reactive center loop‐cleaved crmA to 2.9 Å resolution. The structure, which is the first of a viral serpin, suggests that crmA can inhibit cysteine proteinases by a mechanism analogous to that used by other serpins against serine proteinases. However, one striking difference from other serpins, which may be significant for in vivo function, is an additional highly charged antiparallel strand for β sheet A, whose sequence and length are unique to crmA.