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ISSN
1672-9145
Acta Biochim Biophys Sin
2005, 37(5): 283–292 CN 31-1940/Q
Structural Features and Molecular Evolution of Bowman-Birk Protease
Inhibitors and Their Potential Application
Rui-Feng QI1,2, Zhan-Wu SONG1, and Cheng-Wu CHI2,3*
1College of Life Science, Northwest Normal University, Lanzhou
730070, China;
2Institute of Biochemistry and Cell Biology, Chinese Academy of
Sciences, Shanghai 200031, China;
3Institute of Protein Research, Tongji University, Shanghai 200092,
China
Abstract The Bowman-Birk
inhibitors (BBIs) are well-studied serine protease inhibitors that are abundant
in dicotyledonous and monocotyledonous plants. BBIs from dicots usually have a
molecular weight of 8k and are double-headed with two reactive sites, whereas
those from monocots can be divided into two classes, one approximately 8 kDa in
size with one reactive site (another reactive site was lost) and the other
approximately 16 kDa in size with two reactive sites. The reactive site is
located at unique exposed surfaces formed by a disulfide-linked b-sheet loop that
is highly conserved, rigid and mostly composed of nine residues. The structural
features and molecular evolution of inhibitors are described, focusing on the
conserved disulfide bridges. The sunflower trypsin
inhibitor-1 (SFTI-1),
with 14 amino acid residues, is a recently discovered bicyclic inhibitor, and
is the most small and potent naturally occurring Bowman-Birk inhibitor.
Recently, BBIs have become a hot topic because of their potential applications.
BBIs are now used for defense against pathogens and insects in transgenic
plants, which has advantages over using toxic and polluting insecticides. BBIs
could also be applied in the prevention of cancer, Dengue fever, and
inflammatory and allergic disorders, because of their inhibitory activity with
respect to the serine proteases that play a pivotal role in the development
and pathogenesis of these diseases. The canonical
nine-residue loop of BBIs/STFI-1 provides an ideal template for
drug design of specific inhibitors to target their respective proteases.
Key words Bowman-Birk protease
inhibitor; sunflower trypsin inhibitor-1 (SFTI-1); molecular evolution; drug design
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Received: February 28, 2005 Accepted: March 11, 2005
*Corresponding author: Tel, 86-21-54921165; Fax, 86-21-54921011;
E-mail, [email protected]