title: Crystal structure of viral serpin crmA provides insights into its mechanism of cysteine proteinase inhibition.
abstract: 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 A 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 b sheet A, whose sequence and length are unique to crmA.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Illinois at Chicago, 60612-7334, USA.
authors.forename: M
authors.initials: M
authors.lastname: Simonovic
authors.lastname: Gettins PGW
authors.forename: K
authors.initials: K
authors.lastname: Volz
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray / Q000379:methods; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000737:chemistry* / Q000235:genetics; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D015853:Cysteine Proteinase Inhibitors; D015843:Serpins; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor