Serpins in unicellular Eukarya, Archaea, and Bacteria: Sequence analysis and evolution

Thomas H. Roberts, Jørn Hejgaard, Neil F W Saunders, Ricardo Cavicchioli, Paul M G Curmi

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49 Citations (Scopus)


Most serpins irreversibly inactivate specific serine proteinases of the chymotrypsin family. Inhibitory serpins are unusual proteins in that their native structure is metastable, and rapid conversion to a relaxed state is required to trap target enzymes in a covalent complex. The evolutionary origin of the serpin fold is unresolved, and while serpins in animals are known to be invovled in the regulation of a remarkable diversity of metabolic processes, the physiological functions of homologues from other phyla are unknown. Addressing these questions, here we analyze serpin genes identified in unicellular eukaryotes: the green alga Chlamydomonas reinhardtii, the dinoflagellate Alexandrium tamarense, and the human pathogens Entamoeba spp., Eimera tenella, Toxoplasma gondii, and Giardia lamblia. We compare these sequences to others, particularly those in the complete genome sequences of Archaea, where serpins were found in only 4 of 13 genera, and Bacteria, in only 9 of 56 genera. The serpins from unicellular organisms appear to be phylogenetically distinct from all of the clades of higher eukaryotic serpins. Most of the sequences from unicellular organisms have the characteristics of inhibitory serpins, and where multiple serpin genes are found in one genome, variability is displayed in the region of the reactive-center loop important for specificity. All the unicellular eukaryotic serpins have large hydrophoic or positively charged residues at the putative P1 position. In contrast, none of the prokaryotic serpins has a residue of these types at the predicted P1 position, but many have smaller, neutral residues. Serpin evolution is discussed.

Original languageEnglish
Pages (from-to)437-447
Number of pages11
JournalJournal of Molecular Evolution
Issue number4
Publication statusPublished - Oct 2004


  • Codon usage
  • Genome
  • Green alga
  • Phylogeny
  • Prokaryote
  • Protease
  • Protein fold
  • Proteinase
  • Protostome-deuterostome split
  • Reactive-center loop


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