Bibliography

Bowman-Birk Inhibitors and the Discovery of SFTI-1 next up previous contents
Next: Sequence and Structure Up: SFTI Previous: SFTI

Bowman-Birk Inhibitors and the Discovery of SFTI-1

SFTI-1 is a 14 amino acid, cyclic peptide found in the seeds of Helianthus annus (sunflower) that is a potent inhibitor of trypsin [9,8]. Intriguingly, SFTI-1 belongs to a class of Cys-rich trypsin inhibitors called the Bowman-Birk Inhibitors (BBI) that are widely distributed within plants of the Fabaceae (leguminous) and Poaceae (graminaceous) families [78,77]. BBIs from the Fabaceae generally have a molecular weight of $ \sim$ 8000 while monocot BBIs, from the Poaceae, can be divided into two classes -- one of size $ \sim$ 8000 and the other of $ \sim$ 16000. The smaller monocot BBIs have a single active site, while the dicot BBIs and the larger monocot family both have two reactive loops, in most cases, one targeting trypsin and one targeting chymotrypsin [79]. The duplication of active loops in this class of protein has led to them being referred to as ``double headed'' proteins -- capable of inhibiting trypsin and chymotrypsin in a 1:1:1 stoichiometry simultaneously [80]. SFTI-1 shares strong sequence homology with the trypsin inhibitory loop of the BBI family, suggesting that this peptide may be a minimised version of an ancestral BBI protein.

SFTI-1 was first reported at a conference in Italy where it was described as an unidentified, M$ _r$ 1.5 kDa trypsin inhibitor [81]. Subsequently this inhibitor was named SFTI-1 and its crystal structure in complex with trypsin was described [9]. As was the case with the cyclotides, early attempts to sequence the peptide were frustrated by the lack of an N-terminus. In this case the sequence and cyclic nature of SFTI-1 were eventually determined using a combination of amino acid analysis and sequencing directly from the electron density in the crystal structure [9]. In recent years a great deal of research has centred on the production of minimised polypeptides mimicking the active site of proteins with biologically important activity and the reactive loop of the BBI family has attracted attention as a minimal peptide inhibitor of trypsin [84,82,85,83]. SFTI-1, which appears to be a cyclic version of a BBI trypsin reactive loop, is the most potent known inhibitor of trypsin [8,9].

next up previous contents
Next: Sequence and Structure Up: SFTI Previous: SFTI
Jason Mulvenna
2005-04-24