title: Serpins in prokaryotes.
abstract: Members of the serpin (serine proteinase inhibitor) superfamily have been identified in higher multicellular eukaryotes (plants and animals) and viruses but not in bacteria, archaea, or fungi. Thus, the ancestral serpin and the origin of the serpin inhibitory mechanism remain obscure. In this study we characterize 12 serpin-like sequences in the genomes of prokaryotic organisms, extending this protein family to all major branches of life. Notably, these organisms live in dramatically different environments and some are evolutionarily distantly related. A sequence-based analysis suggests that all 12 serpins are inhibitory. Despite considerable sequence divergence between the proteins, in four of the 12 sequences the region of the serpin that determines proteinase specificity is highly conserved, indicating that these inhibitors are likely to share a common target. Inhibitory serpins are typically prone to polymerization upon heating; thus, the existence of serpins in the moderate thermophilic bacterium Thermobifida fusca, the thermophilic bacterium Thermoanaerobacter tengcongensis, and the hyperthermophilic archaeon Pyrobaculum aerophilum is of particular interest. Using molecular modeling, we predict the means by which heat stability in the latter protein may be achieved without compromising inhibitory activity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Irving
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Steenbakkers
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Lesk
authors.forename: Huub J M
authors.initials: HJ
authors.lastname: Op den Camp
authors.forename: Robert N
authors.initials: RN
authors.lastname: Pike
authors.forename: James C
authors.initials: JC
authors.lastname: Whisstock
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011387:Prokaryotic Cells / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000737:chemistry* / Q000235:genetics; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D015843:Serpins