Proteins of circularly permuted sequence present within the same organism: the major serine proteinase inhibitor from Capsicum annuum seeds

Protein Sci. 2001 Nov;10(11):2280-90. doi: 10.1110/ps.21701.


The major serine proteinase inhibitor from bell pepper (Capsicum annuum, paprika) seeds was isolated, characterized, and sequenced, and its disulfide bond topology was determined. PSI-1.2 is a 52-amino-acid-long, cysteine-rich polypeptide that inhibits both trypsin (K(i) = 4.6 x 10(-9) M) and chymotrypsin (K(i) = 1.1 x 10(-8) M) and is a circularly permuted member of the potato type II inhibitor family. Mature proteins of this family are produced from precursor proteins containing two to eight repeat units that are proteolytically cleaved within, rather than between, the repeats. In contrast, PSI-1.2 corresponds to a complete repeat that was predicted as the putative ancestral protein of the potato type II family. To our knowledge, this is the first case in which two proteins related to each other by circular permutation are shown to exist in the same organism and are expressed within the same organ. PSI-1.2 is not derived from any of the known precursors, and it contains a unique amphiphilic segment in one of its loops. A systematic comparison of the related precursor repeat-sequences reveals common evolutionary patterns that are in agreement with the ancestral gene-duplication hypothesis.

MeSH terms

  • Amino Acid Sequence
  • Capsicum / chemistry*
  • Capsicum / genetics
  • Chymotrypsin / antagonists & inhibitors
  • Disulfides / chemistry
  • Evolution, Molecular
  • Factor Xa Inhibitors
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Phylogeny
  • Sequence Alignment
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / isolation & purification*
  • Thrombin / antagonists & inhibitors
  • Trypsin Inhibitors / isolation & purification


  • Disulfides
  • Factor Xa Inhibitors
  • Serine Proteinase Inhibitors
  • Trypsin Inhibitors
  • Chymotrypsin
  • alpha-chymotrypsin
  • Thrombin

Associated data

  • PDB/1CE3